The increasing hematopoietic effect of the combined treatment of Korean Red Ginseng and Colla corii asini on cyclophosphamide-induced immunosuppression in mice

Yuan Yee Lee,Muhammad Irfan,Yixian Quah,Evelyn Saba,Sung-Dae Kim,Seung-Chun Park,Myung-Gyun Jeong,Yi-Seong Kwak,Man Hee Rhee 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.5

Background: Hematopoiesis is the production of blood cells from hematopoietic stem cells (HSCs) that reside in the bone marrow. Cyclophosphamide (CTX) is a chemotherapy drug that suppresses the immune system. Korean Red Ginseng (KRG) and Colla corii asini (CCA) have been traditionally used for boosting the immune system. Methods: HSCs in the bone marrow, and immune cell subtype in splenocytes, PBMCs, and thymocytes were investigated. Serum levels of hematopoietic-related markers were analyzed using ELISA. Protein expression in spleen tissue was analyzed using western blot analysis. Hematoxylin & eosin staining in the femurs of mice were also conducted. Results: The combination of KRG and CCA with a ratio of 3:2 increased HSCs, CD3 and CD8<SUP>+</SUP> T cells in the circulation, and CD3 T cells in the spleen. A ratio of 2:3 (KRG:CCA) increased the thymic regulatory T cells and recovered the CD3 T cells in the spleen and circulation while recovering proteins in the JAK-STAT pathway in the spleen. Overall, blood cell population and differentiating factors vital for cell differentiation were also significantly recovered by all combinations especially in ratios of 3:2 and 2:3. Conclusion: A ratio of 3:2 (KRG:CCA) is the most ideal combination as it recovered the HSC population in the bone marrow of mice.

COVID-19 and Panax ginseng: Targeting platelet aggregation, thrombosis and the coagulation pathway

Yuan Yee Lee,Yixian Quah,Jung-Hae Shin,Hyuk-Woo Kwon,Dong-Ha Lee,Jee Eun Han,Jin-Kyu Park,Sung Dae Kim,Dongmi Kwak,Seung-Chun Park,Man Hee Rhee 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.2

Coronavirus disease 2019 (COVID-19) not only targets the respiratory system but also triggers a cytokine storm and a series of complications, such as gastrointestinal problems, acute kidney injury, and myocardial ischemia. The use of natural products has been utilized to ease the symptoms of COVID-19, and in some cases, to strengthen the immune system against COVID-19. Natural products are readily available and have been regularly consumed for various health benefits. COVID-19 has been reported to be associated with the risk of thromboembolism and deep vein thrombosis. These thrombotic complications often affects mortality and morbidity. Panax ginseng, which has been widely consumed for its various health benefits has also been reported for its therapeutic effects against cardiovascular disease, thrombosis and platelet aggregation. In this review, we propose that P. ginseng can be consumed as a supplementation against the various associated complications of COVID-19, especially against thrombosis. We utilized the network pharmacology approach to validate the potential therapeutic properties of P. ginseng against COVID-19 mediated thrombosis, the coagulation pathway and platelet aggregation. Additionally, we aimed to investigate the roles of P. ginseng against COVID-19 with the involvement of platelet-leukocyte aggregates in relation to immunity-related responses in COVID-19.

Panax ginseng: Inflammation, platelet aggregation, thrombus formation, and atherosclerosis crosstalk

Yuan Yee Lee,Sung Dae Kim,Seung-Chun Park,Man Hee Rhee 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.1

Ginseng has been widely studied due to its various therapeutic properties on various diseases such as cardiovascular disease (CVD). Cardiovascular disease has been canonically known to be caused by high levels of low-density lipoproteins (LDL) in the bloodstream, in addition to the impaired vasodilatory effects of cholesterol. However, current research on CVD has revealed a cascade of mechanisms involving a series of events that contribute to the progression of CVD. Although this has been elucidated and summarized in previous studies the detailed correlation between platelet aggregation and innate immunity that plays an important role in CVD progression has not been thoroughly summarized. Furthermore, immune cell subtypes also contribute to the progression of plaque formation in the subendothelial layer. Thrombus formation and the coagulation cascade also have a vital role in the progression of atherosclerosis. Hence, in this mini review we aim to elucidate, summarize, and propose the potent therapeutic effect of ginseng on CVD, mainly on platelet aggregation, plaque formation, and thrombus formation.

Antioxidant and Anti-inflammatory Properties of Raw and Processed Fruits and Vegetables

Yuan Yee Lee,Evelyn Saba,Minki Kim,Man Hee Rhee,Hyun-Kyoung Kim 대한의생명과학회 2018 Biomedical Science Letters Vol.24 No.3

Reactive oxygen species (ROS) generated from metabolic reactions cause oxidative DNA damage, which results in oxidative tissue injury. Therefore, there is an increasing demand in the intake of high antioxidant sources in order to maintain a healthy environment in cells. In this study, we investigated the antioxidant and anti-inflammatory activities of Malus domestica (apple), Pyrus communis L. (pear), Daucus carota L. (carrot), Brassica oleracea var. (broccoli), Brassica oleracea var. capitata (cabbage), and Raphanus sativus L. (radish) obtained from the local market. Since these are common fruits and vegetables that are widely consumed, we aimed to investigate their beneficial properties, placing particular emphasis on their antioxidant and anti-inflammatory properties. The samples were processed via an indirect heating method and their properties were compared to their raw forms. Based on DPPH and ABTS assays, processed samples showed better antioxidant activities when compared to raw samples and processed pear samples exhibited the best antioxidant activity. The anti-inflammatory activities of the samples were also investigated in LPS-treated RAW 264.7 cells. mRNA expression of pro-inflammatory mediators and cytokines (iNOS, COX-2, TNF-α, IL-1β, and IL-6) was assessed using RT-PCR. As expected, processed samples exhibited better iNOS inhibition when compared to their raw forms and processed broccoli and cabbage samples exhibited outstanding anti-inflammatory effects. The samples, up to 1 mg/mL concentration, did not exhibit cytotoxicity against RAW 264.7 cells as demonstrated by cell viability assays. Altogether, processed broccoli and cabbage samples exhibited the strongest anti-inflammatory properties.

Physalis alkekengi Exhibits Antiobesity Effects in Mice with Potential of Inducing White Adipose Tissue Browning

Yuan Yee Lee,김민기,Muhammad Irfan,김승형,김성대,MAN HEE RHEE 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.3

The aim of this study was to investigate the efficacy of an ethanol extract of Physalis alkekengi (PA) and its mechanistic pathway of action at the molecular level for its antiobesity properties. Four-week old male Institute of Cancer Research (ICR) mice were acclimatized for a week before starting the high-fat diet (HFD) for 2 weeks to induce obesity, followed by 8 more weeks of oral administration of 10 mg/kg orlistat and 300 mg/kg of PA extract, along with HFD. Body weights of the mice and feed and water intake were recorded weekly. After a total of 12 weeks, mice were euthanized, and blood, liver, and adipose tissues were harvested for further analysis. Administration of PA extract inhibited the progression of obesity by reducing weight gain, weight of adipose tissue, and normalizing serum triglyceride, glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase. PA extract prevented the progression of nonalcoholic steatohepatitis induced by HFD and prevented the enlargement of liver. Phosphorylation of adenosine monophosphate-activated protein kinase α increased while phosphorylation of acetyl-CoA carboxylase was reduced. The browning gene uncoupling protein 1 expression was also increased by PA extract treatment. Our findings revealed that the antiobesity properties of PA extract may be mediated by browning of white adipose tissue.

The anti-platelet activity of panaxadiol fraction and panaxatriol fraction of Korean Red Ginseng in vitro and ex vivo

Yuan Yee Lee,Yein Oh,Min-Soo Seo,Min-Goo Seo,Jee Eun Han,Kyoo-Tae Kim,Jin-Kyu Park,Sung Dae Kim,Sang-Joon Park,Dongmi Kwak,Man Hee Rhee 고려인삼학회 2023 Journal of Ginseng Research Vol.47 No.5

Background: The anti-platelet activity of the saponin fraction of Korean Red Ginseng has been widelystudied. The saponin fraction consists of the panaxadiol fraction (PDF) and panaxatriol fraction (PTF);however, their anti-platelet activity is yet to be compared. Our study aimed to investigate the potency ofanti-platelet activity of PDF and PTF and to elucidate how well they retain their anti-platelet activity viadifferent administration routes. Methods: For ex vivo studies, Sprague-Dawley rats were orally administered 250 mg/kg PDF and PTF for 7consecutive days before blood collection via cardiac puncture. Platelet aggregation was conducted afterisolation of the washed platelets. For in vitro studies, washed platelets were obtained from Sprague-Dawley rats. Collagen and adenosine diphosphate (ADP) were used to induce platelet aggregation. Collagenwas used as an agonist for assaying adenosine triphosphate release, thromboxane B2, serotonin,cyclic adenosine monophosphate, and cyclic guanosine monophosphate (cGMP) release. Results: When treated ex vivo, PDF not only inhibited ADP and collagen-induced platelet aggregation,but also upregulated cGMP levels and reduced platelet adhesion to fibronectin. Furthermore, it alsoinhibited Akt phosphorylation induced by collagen treatment. Panaxadiol fraction did not exert any antiplateletactivity in vitro, whereas PTF exhibited potent anti-platelet activity, inhibiting ADP, collagen, andthrombin-induced platelet aggregation, but significantly elevated levels of cGMP. Conclusion: Our study showed that in vitro and ex vivo PDF and PTF treatments exhibited differentpotency levels, indicating possible metabolic conversions of ginsenosides, which altered the content ofginsenosides capable of preventing platelet aggregation.

A comparative study on immune-stimulatory and antioxidant activities of various types of ginseng extracts in murine and rodent models

Evelyn Saba,Yuan Yee Lee,김민기,김승형,홍승복,MAN HEE RHEE 고려인삼학회 2018 Journal of Ginseng Research Vol.42 No.4

Background: Ginseng (Panax ginseng) is a widely used traditional herbal supplement that possesses various health-enhancing efficacies. Various ginseng products are available in market, especially in the Korean peninsula, in the form of drinks, tablets, and capsules. The different ginseng types include the traditional red ginseng extract (RGE), white ginseng, and black red ginseng extract (BRGE). Their fermented and enzyme-treated products are also available. Different treatment regimens alter the bioavailability of certain compounds present in the respective ginseng extracts. Therefore, in this study, we aimed to compare the antioxidant and immune-stimulating activities of RGE, BRGE, and fermented red ginseng extract (FRGE). Methods: We used an acetaminophen-induced oxidative stress model for investigating the reduction of oxidative stress by RGE, BRGE, and FRGE in Sprague Dawley rats. A cyclophosphamide-induced immunosuppression model was used to evaluate the immune-stimulating activities of these ginseng extracts in BALB/c mice. Results: Our results showed that most prominently, RGE (in almost all experiments) exhibited excellent antioxidant effects via increasing superoxide dismutase, catalase, and glutathione peroxidase activities in the liver and decreasing serum 8-hydroxy-20-deoxyguanosine, aspartate aminotransferase, and lactate dehydrogenase levels compared with the groups treated with FRGE and BRGE. Moreover, RGE significantly increased the number of white blood cells, especially T and B lymphocytes, and antibody-forming cells in the spleen and thymus, and it also activated a number of immune cell subtypes. Conclusion: Taken together, these results indicate that RGE is the best supplement for consumption in everyday life for overall health-enhancing properties.

A novel herbal formulation consisting of red ginseng extract and Epimedium koreanum Nakai-attenuated dextran sulfate sodium-induced colitis in mice

Saba, Evelyn,Lee, Yuan Yee,Kim, Minki,Hyun, Sun-Hee,Park, Chae-Kyu,Son, Eunjung,Kim, Dong-Seon,Kim, Sung-Dae,Rhee, Man Hee The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.6

Background: Ulcerative colitis (UC) is a commonly encountered large intestine disease in the contemporary world that terminates into colorectal cancer; therefore, the timely treatment of UC is of major concern. Panax ginseng Meyer is an extensively consumed herbal commodity in South East Asian countries, especially Korea. It exhibits a wide range of biologically beneficial qualities for almost head-to-toe ailments in the body. Epimedium koreanum Nakai (EKN) is also a widely used traditional Korean herbal medicine used for treating infertility, rheumatism, and cardiovascular diseases. Materials and methods: Separately the anti-inflammatory activities of both red ginseng extracts (RGEs) and EKNs had been demonstrated in the past in various inflammatory models; however, we sought to unravel the anti-inflammatory activities of the combination of these two extracts in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice model because the allopathic remedies for UC involve more side effects than benefits. Results: Our results have shown that the combination of RGE + EKN synergistically alleviated the macroscopic lesions in DSS-induced colitic mice such as colon shortening, hematochezia, and weight loss. Moreover, it restored the histopathological lesions in mice and decreased the levels of proinflammatory mediators and cytokines through the repression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP-3) expression. In vitro, this combination also reduced the magnitude of nitric acid (NO), proinflammatory mediators and cytokine through NF-κB and mitogen-activated protein kinase (MAPK) pathways in RAW 264.7 mouse macrophage cells. Conclusion: In the light of these findings, we can endorse this combination extract as a functional food for the prophylactic as well as therapeutic treatment of UC in humans together with allopathic remedies.

Comparative antiplatelet and antithrombotic effects of red ginseng and fermented red ginseng extracts

Muhammad Irfan,Yuan Yee Lee,Kija Lee,Sung Dae Kim 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.3

Fermentation may alter the bioavailability of certain compounds, which may affect theirefficacy and pharmacological responses. This study investigated the antiplatelet effects of red ginsengextract (RGE) and fermented red ginseng extract (FRG). Methods: A rodent model was used to evaluate the antiplatelet and antithrombotic effects of the extracts. Rats were orally fed with human equivalent doses of the extracts for 1 week and examined for varioussignaling pathways using standard in vivo and ex vivo techniques. Light transmission aggregometry wasperformed, and calcium mobilization, dense granule secretion, integrin aIIbb3-mediated signaling molecules, cyclic nucleotide signaling events, and various protein molecules were evaluated ex vivo incollagen-stimulated washed platelets. Furthermore, antithrombotic properties were evaluated using astandard acute pulmonary thromboembolism model, and the effects on hemostasis were investigatedusing rat and mice models. Results: Both RGE and FRG significantly inhibited platelet aggregation, calcium mobilization, and densegranule secretion along with integrin-mediated fibrinogen binding and fibrinogen adhesion. cAMP levelswere found to be elevated in RGE-treated rat platelets. Ginseng extracts did not exert any effect onprothrombin time and activated partial thromboplastin time. RGE-treated mice showed significantlybetter survival under thrombosis than FRG-treated mice, with no effects on hemostasis, whereas FRGtreated mice exhibited a slight increment in bleeding time. Conclusion: Both extracts, especially RGE, are remarkable supplements to maintain cardiovascular healthand are potential candidates for the treatment and prevention of platelet-related cardiovasculardisorders.

A comparative study on immune-stimulatory and antioxidant activities of various types of ginseng extracts in murine and rodent models

Saba, Evelyn,Lee, Yuan Yee,Kim, Min Ki,Kim, Seung-Hyung,Hong, Seung-Bok,Rhee, Man Hee The Korean Society of Ginseng 2018 Journal of Ginseng Research Vol.42 No.4

Background: Ginseng (Panax ginseng) is a widely used traditional herbal supplement that possesses various health-enhancing efficacies. Various ginseng products are available in market, especially in the Korean peninsula, in the form of drinks, tablets, and capsules. The different ginseng types include the traditional red ginseng extract (RGE), white ginseng, and black red ginseng extract (BRGE). Their fermented and enzyme-treated products are also available. Different treatment regimens alter the bioavailability of certain compounds present in the respective ginseng extracts. Therefore, in this study, we aimed to compare the antioxidant and immune-stimulating activities of RGE, BRGE, and fermented red ginseng extract (FRGE). Methods: We used an acetaminophen-induced oxidative stress model for investigating the reduction of oxidative stress by RGE, BRGE, and FRGE in Sprague Dawley rats. A cyclophosphamide-induced immunosuppression model was used to evaluate the immune-stimulating activities of these ginseng extracts in BALB/c mice. Results: Our results showed that most prominently, RGE (in almost all experiments) exhibited excellent antioxidant effects via increasing superoxide dismutase, catalase, and glutathione peroxidase activities in the liver and decreasing serum 8-hydroxy-2'-deoxyguanosine, aspartate aminotransferase, and lactate dehydrogenase levels compared with the groups treated with FRGE and BRGE. Moreover, RGE significantly increased the number of white blood cells, especially T and B lymphocytes, and antibody-forming cells in the spleen and thymus, and it also activated a number of immune cell subtypes. Conclusion: Taken together, these results indicate that RGE is the best supplement for consumption in everyday life for overall health-enhancing properties.