Antiplatelet and Antithrombotic Activities of Lespedeza cuneata via Pharmacological Inhibition of Integrin αIIbß3, MAPK, and PI3K/AKT Pathways and FeCl3-Induced Murine Thrombosis.

Cardiovascular diseases (CVDs) have been the major cause of mortality all around the globe. Lespedeza cuneata abbreviated as L. cuneata with the authority name of Dumont de Courset (G. Don) is a perennial flowering plant commonly grown in Asian countries such as Korea, Japan, China, and Taiwan. We aimed to investigate the L. cuneata extract's antiplatelet and antithrombotic properties as GC-MS analysis indicated that the extract contained short-chain fatty acids, which have been reported to possess beneficial cardiovascular effects. L. cuneata was extracted using water, 50% EtOH, 70% EtOH, and 100% EtOH. For in vitro antiplatelet analysis, washed platelets were prepared and incubated with L. cuneata with 200 µg/mL of 50% EtOH in the presence of 1 mM of CaCl2 for 1 minute followed by agonist (collagen 2.5 µg/mL or ADP 10 µM or thrombin 0.1 U/mL) stimulation for 5 minutes over light transmission aggregometer. Scanning electron microscopy was performed to assess platelet shape change. ATP release and intracellular calcium mobilization were quantified to assess the granular content. Fibrinogen-binding assay and clot retraction assay assessed integrin αIIbß3-mediated inside-out and outside-in signaling. Protein phosphorylation expression was investigated by western blot analysis. Finally, the in vivo antithrombotic efficacy was investigated by oral dosage of L. cuneata 200 and 400 mg/kg and aspirin 100 mg/kg for 7 days, and tail bleeding and FeCl3-induced murine thrombus model were performed. In vitro platelet aggregation and platelet shape change were dose-dependently suppressed by L. cuneata. Calcium mobilization, dense granules secretion, integrin αIIbß3-mediated inside-out and outside-in signaling, and protein phosphorylation of MAPK and PI3K/Akt pathways were significantly inhibited. In vivo assays revealed that L. cuneata prevents side effects of synthetic drugs via nonsignificantly increasing bleeding time and improving coronary artery blood flow and animal survival. Our results demonstrate that L. cuneata exhibited potent antiplatelet and antithrombotic effects and can be considered a potential herbal medicine with cardioprotective effects.

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

Background: Fermentation may alter the bioavailability of certain compounds, which may affect their efficacy and pharmacological responses. This study investigated the antiplatelet effects of red ginseng extract (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 various signaling pathways using standard in vivo and ex vivo techniques. Light transmission aggregometry was performed, and calcium mobilization, dense granule secretion, integrin αIIbß3-mediated signaling molecules, cyclic nucleotide signaling events, and various protein molecules were evaluated ex vivo in collagen-stimulated washed platelets. Furthermore, antithrombotic properties were evaluated using a standard acute pulmonary thromboembolism model, and the effects on hemostasis were investigated using rat and mice models. Results: Both RGE and FRG significantly inhibited platelet aggregation, calcium mobilization, and dense granule secretion along with integrin-mediated fibrinogen binding and fibrinogen adhesion. cAMP levels were found to be elevated in RGE-treated rat platelets. Ginseng extracts did not exert any effect on prothrombin time and activated partial thromboplastin time. RGE-treated mice showed significantly better survival under thrombosis than FRG-treated mice, with no effects on hemostasis, whereas FRG-treated mice exhibited a slight increment in bleeding time. Conclusion: Both extracts, especially RGE, are remarkable supplements to maintain cardiovascular health and are potential candidates for the treatment and prevention of platelet-related cardiovascular disorders.

Duchesnea indica Extract Ameliorates LPS-Induced Septic Shock in Mice.

Objective: Duchesnea indica has been reported for its anti-inflammatory properties. However, its efficacy in sepsis has yet to be reported. In this study, we studied the ability of Duchesnea indica extract (DIE) to rescue mice from septic shock and sepsis. Methods: In vitro studies included the measurement of secreted nitric oxide, cell viability, gene and protein expression via real-time polymerase chain reaction and western blot, and confocal microscopy in RAW 264.7 cells. In vivo studies include a model of septic shock and sepsis in BALB/c mice induced by a lethal and sub-lethal dose of lipopolysaccharide (LPS). Results: DIE suppressed the expression of proinflammatory cytokines induced by LPS and prevented the translocation of NFκB into the nucleus of RAW 264.7 cells. It also prevented reactive oxygen species damage induced by LPS in murine bone marrow-derived macrophages. Models of sepsis and septic shock were established in BALB/c mice and DIE-rescued mice from septic shock. DIE also reversed the increase in tumor necrosis factor-α and nitrite levels in the serum of mice induced with sepsis. DIE also prevented the translocation of NFκB from the cytosol into the nucleus in murine lungs. Histopathological damage induced by sepsis was reversed in the testis, liver, and lungs of mice. Conclusion: In conclusion, DIE is a suitable candidate for development as a therapeutic agent for sepsis.

Petasites japonicus extract exerts anti-malarial effects by inhibiting platelet activation.

BACKGROUND: New antimalarial agents are needed to combat emerging resistance to the currently available drugs. In the pathology of cerebral malaria, platelets play a central role by binding infected and uninfected red cells and the endothelium. Since Petasites japonicus extract was reported as an effective inhibitor of platelet activation, we examined the antimalarial activities of the P. japonicus extract. PURPOSE: This study aimed to evaluate the impact of P. japonicus extract prepared from whole plants on malarial infection. METHODS: The P. japonicus extract were characterized by high-performance liquid chromatography (HPLC) profiling. Antimalarial activity of the P. japonicus ethanolic extract was evaluated in vitro using chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) P. berghei strains. Also, the in vivo activity of the extract was evaluated in P. berghei-infected mice via oral administration followed by a four-day suppressive test to measure the hematological parameters. In addition, platelet activation signaling induced by the P. japonicus extract in P. berghei infection was evaluated. RESULTS: In HPLC study, catechin, rutin, liquiritin, 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 4,5-di-O-caffeoylquinic acid were identified in P. japonicus extract. Exposure to the P. japonicus extract significantly inhibited both CQ-sensitive (3D7) and resistant (Dd2) strains of P. falciparum with IC50 values of 8.48 ± 1.70 and 7.83 ± 6.44 µg/ml, respectively. Administration of the P. japonicus extract also resulted in potent antimalarial activities in P. berghei-infected mice with no associated toxicity. The treatment also improved the hematologic parameters. In addition, the survived mice from P. berghei infection exhibited the inhibition of collagen-induced platelet aggregation by attenuated glycoprotein VI (GPVI) downstream signaling. CONCLUSION: P. japonicus extracts promote antimalarial effects both in vitro and in vivo. In addition, the effects appear to be induced by the inhibition of collagen-induced platelet activation related to attenuated GPVI downstream signaling. Further studies to identify and characterize the antimalarial compounds in P. japonicus will promote the development of new drugs.

Rumex acetosella Inhibits Platelet Function via Impaired MAPK and Phosphoinositide 3-Kinase Signaling.

OBJECTIVE: To examine the antiplatelet and antithrombotic activity of Rumex acetosella extract. METHODS: Standard light aggregometry was used for platelet aggregation, intracellular calcium mobilization assessed using Fura-2/AM, granule secretion (ATP release) by luminometer, and fibrinogen binding to integrin αIIbß3 detected using flow cytometry. Western blotting is carried out to determine the phosphorylation of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt signaling. RESULTS: Rumex acetosella displayed the ability to inhibit platelet aggregation, calcium mobilization, granule secretion, and fibrinogen binding to integrin αIIbß3. Rumex acetosella has also down-regulated MAPK and PI3K/Akt phosphorylation (all P<0.01). CONCLUSION: Rumex acetosella extract exhibits antiplatelet activity via modulating GPVI signaling, and it may protect against the development of platelet-related cardiovascular diseases.

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

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+ 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.

Inhibitory Effect of Phellinus baumii Extract on CFA-Induced Inflammation in MH-S Cells through Nuclear Factor-κB and Mitogen-Activated Protein Kinase Signaling Pathways.

Phellinus baumii is a mushroom utilized as a traditional medicine for a wide range of human ailments, including diabetes, hypertension, hypercholesterolemia, and cancer, in Asia. The purpose of this study was to find out whether Phellinus baumii extract (PBE) could reduce inflammation caused by coal fly ash (CFA) in alveolar macrophages (MH-S). The anti-inflammatory effect of PBE was evaluated by measuring the nitric oxide (NO) concentration after the onset of CFA-stimulated inflammation in MH-S cells. Polymerase chain reaction (PCR) was used to examine inflammatory gene expression. Western blotting and immunofluorescence (IF) studies were used to investigate the inflammatory mechanism in MH-S cells. According to our results, the PBE suppressed CFA-induced NO generation in the MH-S cells dose-dependently. Furthermore, PBE inhibited the proinflammatory mediators and cytokines generated by exposure to CFA, including cyclooxygenase 2 (COX-2) and inducible NO synthase (iNOS), interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α). Real-time PCR was also used to determine the inhibiting effect of the PBE on proinflammatory factors such as COX-2, iNOS, IL-1ß, IL-6, and TNF-α. Moreover, Western blot was used to assess the effects of the PBE on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in the CFA-stimulated MH-S cells. The suppressive effect of the PBE on phosphorylated (p)-NF-κB translocation was also investigated using IF analysis. This study showed that the PBE suppressed the CFA-induced inflammation in the MH-S cells by suppressing the NF-κB and MAPK signaling pathways, which suggests its potential usefulness in reducing lung inflammation.

In Vitro Antiplatelet Activity of Mulberroside C through the Up-Regulation of Cyclic Nucleotide Signaling Pathways and Down-Regulation of Phosphoproteins.

Physiological agonists trigger signaling cascades, called "inside-out signaling", and activated platelets facilitate adhesion, shape change, granule release, and structural change of glycoprotein IIb/IIIa (αIIb/ß3). Activated αIIb/ß3 interacts with fibrinogen and begins second signaling cascades called "outside-in signaling". These two signaling pathways can lead to hemostasis or thrombosis. Thrombosis can occur in arterial and venous blood vessels and is a major medical problem. Platelet-mediated thrombosis is a major cause of cardiovascular disease (CVD). Therefore, controlling platelet activity is important for platelet-mediated thrombosis and cardiovascular diseases. In this study, focus on Morus Alba Linn, a popular medicinal plant, to inhibit the function of platelets and found the containing component mulberroside C. We examine the effect of mulberroside C on the regulation of phosphoproteins, platelet-activating factors, and binding molecules. Agonist-induced human platelet aggregation is dose-dependently inhibited by mulberroside C without cytotoxicity, and it decreased Ca2+ mobilization and p-selectin expression through the upregulation of inositol 1, 4, 5-triphosphate receptor I (Ser1756), and downregulation of extracellular signal-regulated kinase (ERK). In addition, mulberroside C inhibited thromboxane A2 production, fibrinogen binding, and clot retraction. Our results show antiplatelet effects and antithrombus formation of mulberroside C in human platelets. Thus, we confirm that mulberroside C could be a potential phytochemical for the prevention of thrombosis-mediated CVDs.

Duchesnea indica Extract Attenuates Coal Fly Ash-Induced Inflammation in Murine Alveolar Macrophages through the NF-Kappa B Pathway.

Duchesnea indica is known as false strawberry, is found in East Asia, and has numerous biological properties. The aim of this study was to investigate the anti-inflammatory effect of Duchesnea indica extract (DIE) on coal fly ash- (CFA-) induced inflammation in murine alveolar macrophages (MH-S). Following the induction of inflammation in MH-S cells by CFA, nitric oxide (NO) was measured to evaluate the anti-inflammatory property of DIE. Cell viability and inflammatory gene expression were analyzed using polymerase chain reaction (PCR). The inflammatory pathway in MH-S cells was determined via western blotting and immunofluorescence (IF) analysis. Finally, the major components of the DIE were identified and separated through ultra-performance liquid chromatography (UPLC) and gas chromatography-mass spectrometry (GC-MS) analysis. Our results showed that the DIE dose-dependently inhibited the CFA-induced NO production in MH-S cells. Moreover, the DIE could suppress the CFA-induced proinflammatory mediators, such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In addition, the inhibitory effect of the DIE on proinflammatory cytokines, including interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α), was detected with PCR. Moreover, the effect of the DIE on the nuclear factor-κB (NF-κB) pathway in CFA-activated MH-S cells was measured via western blotting. Furthermore, the inhibition of the phosphorylated NF-κB (p-NF-κB) translocation was analyzed using IF assay. The findings of this study indicated that the DIE potentially inhibited the CFA-induced inflammation by blocking the NF-κB inflammatory signaling pathway in MH-S cells and that the DIE might contain favorable anti-inflammatory compounds which may be effective in attenuating lung inflammation.

Red Ginseng Oil Attenuates Oxidative Stress and Offers Protection against Ultraviolet-Induced Photo Toxicity.

Ginseng (Panax ginseng Meyer) is a well-known herbal medicine that has been used for a long time in Korea to treat various diseases. This study investigated the in vitro and in vivo protective effects of red ginseng extract (RGE) and red ginseng oil (RGO). Liver injury was produced in BALB/c mice by 400 mg/kg of acetaminophen intraperitoneal injection. The antioxidant effects of RGE and RGO on the free radicals 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) were measured. In addition, the hepatoprotective activities of RGE and RGO on liver markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and oxidative stress markers, including superoxide dismutase (SOD), catalase (CAT) enzyme activity, and 8-hydroxy-2-deoxyguanosine (8-OHdG) in serum and histopathological analysis, were evaluated. The protective effect of RGO on UV-induced phototoxicity was also evaluated in Balb/c 3T3 mouse fibroblast cell line. RGE and RGO effectively inhibited the radicals DPPH and ABTS compared with ascorbic acid and trolox, respectively. Moreover, RGE and RGO significantly decreased the liver enzyme (ALT and AST) levels, increased the antioxidant enzyme (SOD and CAT) levels, and decreased the DNA oxidation product (8-OHdG) content in mice serum. RGO also exhibited protective effect against UV irradiation compared with chlorpromazine hydrochloride, a known phototoxic drug, in Balb/c 3T3 cell line. RGE and RGO possess antioxidant and hepatoprotective properties in mice, and RGO exerts nonphototoxic activity in Balb/c 3T3 cells.

Antiplatelet and Antithrombotic Effects of Epimedium koreanum Nakai.

Background and Objective. Epimedium koreanum Nakai is a medicinal plant known for its health beneficial effects on impotence, arrhythmia, oxidation, aging, osteoporosis, and cardiovascular diseases. However, there is no report available that shows its effects on platelet functions. Here, we elucidated antiplatelet and antithrombotic effects of ethyl acetate fraction of E. koreanum. Methodology. We analyzed the antiplatelet properties using standard in vitro and in vivo techniques, such as light transmission aggregometry, scanning electron microscopy, intracellular calcium mobilization measurement, dense granule secretion, and flow cytometry to assess integrin α IIb ß 3 activation, clot retraction, and Western blot, on washed platelets. The antithrombotic effects of E. koreanum were assessed by arteriovenous- (AV-) shunt model in rats, and its effects on hemostasis were analyzed by tail bleeding assay in mice. Key Results. E. koreanum inhibited platelet aggregation in agonist-stimulated human and rat washed platelets, and it also reduced calcium mobilization, ATP secretion, and TXB2 formation. Fibrinogen binding, fibronectin adhesion, and clot retraction by attenuated integrin α IIb ß 3-mediated inside-out and outside-in signaling were also decreased. Reduced phosphorylation of extracellular signal-regulated kinases (ERK), Akt, PLCγ2, and Src was observed. Moreover, the fraction inhibited thrombosis. HPLC results revealed that the fraction predominantly contained icariin. Conclusion and Implications. E. koreanum inhibited platelet aggregation and thrombus formation by attenuating calcium mobilization, ATP secretion, TXB2 formation, and integrin α IIb ß 3 activation. Therefore, it may be considered as a potential candidate to treat and prevent platelet-related cardiovascular disorders.

Corrigendum to "A novel herbal formulation consisting of red ginseng extract and Epimedium koreanum Nakai-attenuated dextran sulfate sodium induced colitis in mice" [J Ginseng Res 44 (2020) 833-842].

[This corrects the article DOI: 10.1016/j.jgr.2020.02.003.].

Antimalarial Effect of the Total Glycosides of the Medicinal Plant, Ranunculus japonicus.

In traditional Chinese medicine, Ranunculus japonicus has been used to treat various diseases, including malaria, and the young stem of R. japonicus is consumed as a food in the Republic of Korea. However, experimental evidence of the antimalarial effect of R. japonicus has not been evaluated. Therefore, the antimalarial activity of the extract of the young stem of R. japonicus was evaluated in vitro using both chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains; in vivo activity was evaluated in Plasmodium berghei-infected mice via oral administration followed by a four-day suppressive test focused on biochemical and hematological parameters. Exposure to extracts of R. japonicus resulted in significant inhibition of both chloroquine-sensitive (3D7) and resistant (Dd2) strains of P. falciparum, with IC50 values of 6.29 ± 2.78 and 5.36 ± 4.93 µg/mL, respectively. Administration of R. japonicus also resulted in potent antimalarial activity against P. berghei in infected mice with no associated toxicity; treatment also resulted in improved hepatic, renal, and hematologic parameters. These results demonstrate the antimalarial effects of R. japonicus both in vitro and in vivo with no apparent toxicity.

Derrone Inhibits Platelet Aggregation, Granule Secretion, Thromboxane A2 Generation, and Clot Retraction: An In Vitro Study.

Cudrania tricuspidata (C. tricuspidata) is widespread throughout East Asia and in China and Korea, and it is widely used as a traditional remedy against eczema, mumps, and tuberculosis. With regard to the aforementioned medical efficacy, various studies are continuously being conducted, and it has been reported that C. tricuspidata extract has various actions against inflammation, diabetes, obesity, and tumors. Therefore, we evaluated antiplatelet effects using derrone in C. tricuspidata. We examined the effect of derrone on the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and inositol 1, 4, 5-triphosphate receptor I (IP3RI), and on the dephosphorylation of cytosolic phospholipase A2 (cPLA2), mitogen-activated protein kinases p38 (p38MAPK), and Akt, which affects platelet function and thrombus formation. Various agonists-induced human platelets were inhibited by derrone without cytotoxicity, and it also decreased the intracellular calcium level through the signaling molecule phosphorylations. In addition, derrone inhibited glycoprotein IIb/IIIa (αIIb/ß3) affinity. Thus, in the present study, derrone suppressed human platelet aggregation and thrombin-induced clot formation.

Hypericum ascyron L. extract reduces particulate matter-induced airway inflammation in mice.

The consequences of increased industrialization increased the risk of asthma and breathing difficulties due to increased particulate matter in the air. We aim to investigate the therapeutic properties of Hypericum ascyron L. extract (HAE) in airway inflammation and unravel its mechanism of action. We conducted nitric oxide and cell viability assay, real-time PCR and western blot analyses along with in vitro studies. in vivo studies include a model of coal fly ash and diesel exhaust particle (CFD)-induced airway inflammation in mice. HAE reduced coal fly ash (CFA)-induced nitric oxide secretion without exhibiting cytotoxicity in MH-S cells. HAE also reduced the mRNA expression of pro-inflammatory cytokines and reduced the expression of proteins in the NFκB and MAPK pathways. In a mice model of CFD-induced airway inflammation, HAE effectively reduced neutrophil infiltration in bronchoalveolar lavage fluid (BALF) and increased the amount of T cells in the BALF, lungs, and blood while reducing all other immune cell subtypes to reduce airway inflammatory response. CXCL-1, IL-17, MIP-2, and TNF-α expression in the BALF were also reduced. HAE effectively reduced MIP-2 and TNF-α mRNA expression in the lung tissue of mice. In a nutshell, HAE is effective in preventing airway inflammation induced by CFA in MH-S cells, as well as inflammation induced by CFD in mice.

Alleviation of Ulcerative Colitis Potentially through th1/th2 Cytokine Balance by a Mixture of Rg3-enriched Korean Red Ginseng Extract and Persicaria tinctoria.

Ginseng is a vastly used herbal supplement in Southeast Asian countries. Red ginseng extract enriched with Rg3 (Rg3-RGE) is a formula that has been extensively studied owing to its various biological properties. Persicaria tinctoria (PT), belonging to the Polygonaceae family, has also been reported for its anti-inflammatory properties. Ulcerative colitis (UC) is inflammation of the large intestine, particularly in the colon. This disease is increasingly common and has high probability of relapse. We investigated, separately and in combination, the effects of Rg3-RGE and PT using murine exemplary of UC induced by DSS (Dextran Sulfate Sodium). For in vitro and in vivo experiments, nitric oxide assay, qRT-Polymerase Chain Reaction (PCR), Western blot, ulcerative colitis introduced by DSS, Enzyme Linked Immunosorbent Assay (ELISA), and flow cytometry analysis were performed. The results obtained demonstrate that treatment with Rg3-RGE + PT showed synergism to suppress inflammation (in vitro) in RAW 264.7 cells via mitogen-activated protein kinase and nuclear factor κB pathways. Moreover, in C57BL/6 mice, this mixture exhibits strong anti-inflammatory effects in restoring colon length, histopathological damage, pro-inflammatory mediators, and cytokines amount, and decreasing levels of NLRP3 inflammasome (in vivo). Our results recommend that this mixture can be used for the prevention of UC as a prophylactic/therapeutic supplement.

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

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 pro-inflammatory 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), pro-inflammatory 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.

Anti-Melanogenic Effects of Korean Red Ginseng Oil in an Ultraviolet B-Induced Hairless Mouse Model.

A 'remedy for all' natural product widely known in the Korean Peninsula is called Panax Ginseng Meyer. Globalization represents a persistent risk to the ozone layer, leading to bountiful amounts of Ultra-Violet B beams (UVB). The variety in human skin hues is ascribed to the characteristic color called Melanin. However, Melanin overproduction due to UVB beams promotes skin staining and tumorigenesis, a process called photo aging, which damages skin quality. To assess the effects of Korean Red Ginseng Oil (KGO) on photo aging, the murine melanoma cell lines B16/F10 were used in vitro and HRM-2 hairless mice exposed to UVB were studied in vivo. Our results revealed that KGO reduced tyrosinase activity and melanin production in B16/F10 cells along with the suppression of upstream factors involved in the melanin production pathway, both transcriptionally and transitionally. In the in vivo studies, KGO suppressed the expression of Matrix Metalloproteinase (MMP) and Interleukins along with a reduction of depth in wrinkle formation and reduced collagen degradation. Moreover, the feed intake and feed efficiency ratio that decreased as a result of UVB exposure was also improved by KGO treatment. In light of our results, we conclude that KGO can have considerable benefits due to its various properties of natural skin enhancement.

Effects of a herbal formulation, KGC3P, and its individual component, nepetin, on coal fly dust-induced airway inflammation.

Coal fly dust (CFD)-induced asthma model is used as an ambient particulate matter model of serious pulmonary damage. We aimed to evaluate the effects of a combination of ginseng and Salvia plebeia R. Br extract (KGC-03-PS; KG3P) and its individual components (hispidulin, nepetin and rosmarinic acid) in a CFD-induced mouse model of airway inflammation (asthma). We also evaluated signal transduction by KG3P and its individual components in the alveolar macrophage cell line, MH-S cells. In vitro, KG3P and its individual components inhibited nitric oxide production and expression of pro-inflammatory mediators and cytokines (iNOS, COX-2, IL-1ß, IL-6 and TNF-α) through the NF-κB and MAPK pathways in coal fly ash (CFA)-induced inflammation in MH-S cells. Moreover, in the CFD-induced asthma model in mice, KG3P and its predominant individual component, nepetin, inhibited Asymmetric Dimethyl arginine (ADMA) and Symmetric Dimethyl arginine (SDMA) in serum, and decreased the histopathologic score in the lungs. A significant reduction in the neutrophils and immune cells in BALF and lung tissue was demonstrated, with significant reduction in the expression of the pro-inflammatory cytokines. Finally, IRAK-1 localization was also potently inhibited by KG3P and nepetin. Thus, KG3P extract can be considered as a potent candidate for amelioration of airway inflammation.

Adaptogenic effects of Panax ginseng on modulation of cardiovascular functions.

Cardiovascular diseases are a rapidly growing epidemic with high morbidity and mortality. There is an urgent need to develop nutraceutical-based therapy with minimum side effects to reduce cardiovascular risk. Panax ginseng occupies a prominent status in herbal medicine for its various therapeutic effects against inflammation, allergy, diabetes, cardiovascular diseases, and even cancer, with positive, beneficial, and restorative effects. The active components found in most P. ginseng varieties are known to include ginsenosides, polysaccharides, peptides, alkaloids, polyacetylene, and phenolic compounds, which are considered to be the main pharmacologically active constituents in ginseng. P. ginseng is an adaptogen. That is, it supports living organisms to maintain optimal homeostasis by exerting effects that counteract physiological changes caused by physical, chemical, or biological stressors. P. ginseng possesses immunomodulatory (including both immunostimulatory and immunosuppressive), neuromodulatory, and cardioprotective effects; suppresses anxiety; and balances vascular tone. P. ginseng has an antihypertensive effect that has been explained by its vasorelaxant action, and paradoxically, it is also known to increase blood pressure by vasoconstriction and help maintain cardiovascular health. Here, we discuss the potential adaptogenic effects of P. ginseng on the cardiovascular system and outline a future research perspective in this area.