PMID: 

J Food Sci. 2011 Mar ;76(2):C250-6. Epub 2011 Feb 3. PMID: 21535743

Abstract Title: 

Neuroprotective effect of caffeoylquinic acids from Artemisia princeps Pampanini against oxidative stress-induced toxicity in PC-12 cells.

Abstract: 

Phenolics in dry Artemisia princeps Pampanini, an herbal plant traditionally consumed as food ingredients in Korea was extracted, fractionated, and quantified as well as evaluated for its neuroprotection for PC-12 cells. Whole extract had 5,852 mg gallic acid equivalents/100 g of total phenolics and 6,274 mg and 9,698 mg vitamin C equivalents/100 g of antioxidant capacities assayed by DPPH and ABTS radicals, respectively. The fraction extracted with n-butanol had the highest levels of total phenolics and antioxidant capacity than the other fractions (n-hexane, chloroform, ethyl acetate, and water). Using a reversed-phase HPLC system, caffeoylquinic acid (CQA) and its derivatives such as 3-CQA, 4-CQA, 5-CQA, 1,5-diCQA, 3,4-diCQA, 3,5-diCQA, and 4,5-diCQA were isolated and quantified. The whole extract and its n-butanol fraction yielded 3,5-diCQA with the highest amount, which consisted of approximately 36.8% and 33.5%, respectively. The whole extract, the n-butanol fraction, and 3,5-diCQA showed neuroprotective effect on PC-12 cells under the insult of amyloidß peptide in a dose-dependent manner. Treatments of the whole extract and the n-butanol fraction for PC-12 cells under oxidative stress increased approximately 1.6 and 2.4 times higher cell viability, compared with the control without treatments. For PC-12 cells treated with 3,5-diCQA, intracellular oxidative stress decreased by 51.3% and cell viability increased up to 2.8 times compared to the control with oxidative insult of amyloid ß peptide only. These results indicate that phenolics from A. princeps Pampanini alleviated the oxidative stress and enhanced the viability of PC-12 cells, suggesting that it may be applied as a dietary antineurodegenerative agent in functional foods.

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PMID: 

J Virol. 2018 09 1 ;92(17). Epub 2018 Aug 16. PMID: 29925653

Abstract Title: 

Newcastle Disease Virus-Based Vectored Vaccine against Poliomyelitis.

Abstract: 

The poliovirus eradication initiative has spawned global immunization infrastructure and dramatically decreased the prevalence of the disease, yet the original virus eradication goal has not been met. The suboptimal properties of the existing vaccines are among the major reasons why the program has repeatedly missed eradication deadlines. Oral live poliovirus vaccine (OPV), while affordable and effective, occasionally causes the disease in the primary recipients, and the attenuated viruses rapidly regain virulence and can cause poliomyelitis outbreaks. Inactivated poliovirus vaccine (IPV) is safe but expensive and does not induce the mucosal immunity necessary to interrupt virus transmission. While the need for a better vaccine is widely recognized, current efforts are focused largely on improvements to the OPV or IPV, which are still beset by the fundamental drawbacks of the original products. Here we demonstrate a different design of an antipoliovirus vaccine based onproduction of virus-like particles (VLPs). The poliovirus capsid protein precursor, together with a protease required for its processing, are expressed from a Newcastle disease virus (NDV) vector, a negative-strand RNA virus with mucosal tropism. In this system, poliovirus VLPs are produced in the cells of vaccine recipients and are presented to their immune systems in the context of active replication of NDV, which serves as a natural adjuvant. Intranasal administration of the vectored vaccine to guinea pigs induced strong neutralizing systemic and mucosal antibody responses. Thus, the vectored poliovirus vaccine combines the affordability and efficiency of a live vaccine with absolute safety, since no full-length poliovirus genome is present at any stage of the vaccine life cycle.A new, safe, and effective vaccine against poliovirus is urgently needed not only to complete the eradication of the virus but also to be used in the future to prevent possible virus reemergence in a postpolio world. Currently, new formulations of the oral vaccine, as well as improvements to the inactivated vaccine, are being explored. In this study, we designed a viral vector with mucosal tropism that expresses poliovirus capsid proteins. Thus, poliovirus VLPs are produced, in the cells of a vaccine recipient, and are presented to the immune system in the context of vector virus replication, stimulating the development of systemic and mucosal immune responses. Such an approach allows the development of an affordable and safe vaccine that does not rely on the full-length poliovirus genome at any stage.

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PMID: 

Semin Neurol. 2002 Mar ;22(1):95-8. PMID: 12170398

Abstract Title: 

The smallpox vaccine and postvaccinal encephalitis.

Abstract: 

Smallpox is one of the deadliest infectious diseases in history. The discovery by Edward Jenner that inoculation with a droplet of pus from a cow with cowpox protected a person from smallpox resulted in the successful vaccination of millions of people. There were, however, complications associated with smallpox vaccination; the most serious complication was postvaccinal encephalitis, which was reported to occur with an incidence of 1 in 110,000 vaccinations and a case-fatality rate of 50%. Before we become complacent with the idea that we will respond to a bioterrorism attack with a mass immunization program for smallpox, it is important to be reminded of the risk and clinical manifestations of postvaccinal encephalitis and the efficacy of antivaccinia gamma-globulin in preventing this complication. The first case of postvaccinal encephalitis as a complication of the Jennerian cowpox inoculation was observed in 1905. A century later, there is no effective therapy.

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PMID: 

J Ethnopharmacol. 2012 May 7 ;141(1):460-8. Epub 2012 Mar 18. PMID: 22449440

Abstract Title: 

Standardized flavonoid-rich fraction of Artemisia princeps Pampanini cv. Sajabal induces apoptosis via mitochondrial pathway in human cervical cancer HeLa cells.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia princeps Pampanini is widely used in Eastern traditional medicine for the treatment of circulatory disorders, such as, dysmenorrhea, hematuria, hemorrhoids, and inflammation, and is also used to treat chronic conditions, such as, cancers, ulcers, and digestive disorders.AIM OF THE STUDY: The purpose of this study is to investigate the effect of a standardized flavonoid-rich fraction of Artemisia princeps Pampanini cv. Sajabal (FRAP) on the induction of apoptosis and the molecular mechanism involved in human cervical cancer HeLa cells.MATERIALS AND METHODS: Human cervical cancer HeLa cells were treated with FRAP and apoptosis was detected by cell morphologic observation, annexin-V-PI staning and western blot analysis on the expression of protein associated with cell death.RESULTS: FRAP led to the cleavages of caspase-3, -8, and -9 and the cleavage of poly (ADP-ribose) polymerase (PARP) in HeLa cells. Caspase-3 inhibitor (z-DEVD-fmk), caspase-8 inhibitor (z-IETD-fmk), caspase-9 inhibitor (z-LEHD), and broad caspase inhibitor (z-VAD-fmk) significantly suppressed the FRAP-induced accumulation of annexin V positive cells. Furthermore, it was found that FRAP caused a loss of mitochondrial membrane potential (MMP) and the release of cytochrome c to the cytosol. Furthermore, the overexpression of Bcl-xL significantly prevented FRAP-induced apoptosis, MMP changes, and the activations of caspase-3, -8, and -9. Interestingly, pretreatment with caspase-8 inhibitor significantly reduced the FRAP-induced activation of caspase-3 but not that of caspase-9, whereas the caspase-3 inhibitor, z-DEVD-fmk, markedly attenuated the FRAP-induced activation of caspase-8. In BALB/c(nu/nu) mice bearing a HeLa xenograft, FRAP dosed at 25 or 50mg/kg significantly inhibited tumor growth.CONCLUSION: Our results indicate caspase-mediated activation of the mitochondrial death pathway plays a critical role in the FRAP-induced apoptosis of HeLa cells and that FRAP inhibits the in vivo tumor growth of HeLa xenograft mice.

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PMID: 

Vaccine. 2014 Jun 30 ;32(31):3886-94. Epub 2014 May 14. PMID: 24837502

Abstract Title: 

Challenges in vaccination of neonates, infants and young children.

Abstract: 

All neonates, infants and young children receive multiple priming doses and booster vaccinations in the 1st and 2nd year of life to prevent infections by viral and bacterial pathogens. Despite high vaccine compliance, outbreaks of vaccine-preventable infections are occurring worldwide. These data strongly argue for an improved understanding of the immune responses of neonates, infants and young children to vaccine antigens and further study of the exploitable mechanisms to achieve more robust and prolonged immunity with fewer primary and booster vaccinations in the pediatric population. This review will focus on our recent work involving infant and young child immunity following routine recommended vaccinations. The discussion will address vaccine responses with respect to four areas: (1) systemic antibody responses, (2) memory B-cell generation, (3) CD4 T-cell responses, and (4) APC function.

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PMID: 

J Ethnopharmacol. 2013 Feb 13 ;145(3):767-75. Epub 2012 Dec 8. PMID: 23228915

Abstract Title: 

Artemisia leaf extract induces apoptosis in human endometriotic cells through regulation of the p38 and NFκB pathways.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia leaves have long been used for the treatment of gynecological disorders, including infertility and dysmenorrhea, which can be commonly caused by endometriosis. In the present study, we investigated the effect of Artemisia princeps extract (APE) on the cell growth and apoptosis of human endometriotic cells.MATERIALS AND METHODS: MTT assays and FACS analysis using PI and Annexin staining were performed to study cell viability, cell cycle progression, and apoptosis. We also explored the mechanism of APE-induced effects by evaluating the activation of caspases, Akt, p38, and NFκB. The expressions of XIAP, Bcl-2, and Bcl-xL were measured by real-time RT-PCR and Western blot analyses.RESULTS: APE significantly inhibited the cell viability of 11Z and 12Z human endometriotic epithelial cells. Interestingly, endometriotic cells were more sensitive to APE treatment than immortalized endometrial cells (HES). Treatment with APE induced apoptosis of 11Z cells in a time-dependent manner, as shown by accumulation of sub G1 and apoptotic cell populations. In addition, treatment with APE stimulated the activation of caspase -3, -8, and -9 in a dose- and time-dependent manner. Furthermore, p38 was activated by APE treatment, and the p38 inhibitor SB203580 markedly inhibited APE-induced cell death in 11Z cells. Moreover, treatment with APE suppressed the activation of NFκB and the expressions of anti-apoptotic factors such as XIAP, Bcl-2, and Bcl-xL.CONCLUSION: These results indicate that APE is a potential anti-endometriotic agent, acting to induce apoptosis of endometrial cells through the modulation of the p38 and NFκB pathways.

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PMID: 

CMAJ. 2015 Apr 7 ;187(6):E180. Epub 2015 Mar 2. PMID: 25733738

Abstract Title: 

Repeated flu shots may blunt effectiveness.

Abstract: 

[n/a]

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PMID: 

Food Chem Toxicol. 2013 May ;55:214-21. Epub 2012 Dec 26. PMID: 23274058

Abstract Title: 

Jaceosidin, isolated from dietary mugwort (Artemisia princeps), induces G2/M cell cycle arrest by inactivating cdc25C-cdc2 via ATM-Chk1/2 activation.

Abstract: 

Jaceosidin, a flavonoid derived from Artemisia princeps (Japanese mugwort), has been shown to inhibit the growth of several human cancer cells, However, the exact mechanism for the cytotoxic effect of jaceosidin is not completely understood. In this study, we investigated the molecular mechanism involved in the antiproliferative effect of jaceosidin in human endometrial cancer cells. We demonstrated that jaceosidin is a more potent inhibitor of cell growth than cisplatin in human endometrial cancer cells. In contrast, jaceosidin-induced cytotoxicity in normal endometrial cells was lower than that observed for cisplatin. Jaceosidin induced G2/M phase cell cycle arrest and modulated the levels of cyclin B and p-Cdc2 in Hec1A cells. Knockdown of p21 using specific siRNAs partially abrogated jaceosidin-induced cell growth inhibition. Additional mechanistic studies revealed that jaceosidin treatment resulted in an increase in phosphorylation of Cdc25C and ATM-Chk1/2. Ku55933, an ATM inhibitor, reversed jaceosidin-induced cell growth inhibition, in part. Moreover, jaceosidin treatment resulted in phosphorylation of ERK, and pretreatment with the ERK inhibitor, PD98059, attenuated cell growth inhibition by jaceosidin. These data suggest that jaceosidin, isolated from Japanese mugwort, modulates the ERK/ATM/Chk1/2 pathway, leading to inactivation of the Cdc2-cyclin B1 complex, followed by G2/M cell cycle arrest in endometrial cancer cells.

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PMID: 

J Pharm Pharmacol. 2009 Aug ;61(8):1043-50. PMID: 19703348

Abstract Title: 

Anti-inflammatory effects of Artemisia princeps in antigen-stimulated T cells and regulatory T cells.

Abstract: 

OBJECTIVES: The aim was to investigate the anti-inflammatory effects of Artemisia princeps extract on the activity of anti-CD3/CD28-stimulated CD4(+)CD25(-) T cells and antigen-expanded regulatory T cells.METHODS: CD4(+)CD25(-) T cells were activated with coated anti-CD3 and anti-CD28 and cultured in the presence or absence of various concentrations of A. princeps extract. The cultures were pulsed on Day 6 with [(3)H]thymidine and, after harvesting the cells, [(3)H]thymidine incorporation was measured. For analysis of interleukin-2 and interferon-gamma secreted from CD4(+)CD25(-) T cells, culture supernatants were collected on Days 2 and 6. For the analysis of interleukin-10 secreted from the CD4(+)CD25(-) T cells and expanded regulatory T cells, supernatants were collected after 2 and 7 days, respectively. Cytokine levels were determined using an enzyme-linked immunosorbent assay. Potential medicinal components of the A. princeps extract were determined using gas chromatography-mass spectrometry.KEY FINDINGS: A. princeps (30 microg/ml) effectively suppressed proliferation of CD4(+)CD25(-) T cells that were stimulated with anti-CD3/CD28 without causing cytotoxicity in spleen cells incubated under conditions lacking antigen stimulation. A. princeps inhibited production of the pro-inflammatory cytokines interleukin-2 and interferon-gamma in anti-CD3/CD28-stimulated CD4(+)CD25(-) T cells. Also, the extract slightly increased production of the anti-inflammatory cytokine interleukin-10 in these cells. In regulatory T cells expanded by anti-CD3/CD28, A. princeps increased production of interleukin-10 and Foxp3.CONCLUSIONS: The results suggest that A. princeps may be useful in the treatment of autoimmune diseases and organ transplantation rejection by inhibiting proliferation of inflammatory T cells, suppressing inflammatory processes in antigen-stimulated CD4(+)CD25(-) T cells and increasing activity of expanded regulatory T cells.

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PMID: 

Anticancer Res. 2007 Nov-Dec;27(6B):3891-8. PMID: 18225547

Abstract Title: 

Artemisia princeps var orientalis induces apoptosis in human breast cancer MCF-7 cells.

Abstract: 

BACKGROUND: Dried leaves of Artemisia princeps var orientalis are used in the Eastern practice of moxibustion to improve general health. The ability of A. princeps smoke and water extracts to induce apoptosis was evaluated in human breast cancer MCF-7 cells in vitro.MATERIALS AND METHODS: Tumor cells were cultured with a smoke or water extract (1.5-50% v/v) for 72 h, and cytotoxicity and apoptosis were determined by MTT and TUNEL assays, respectively. Activation of caspases, changes in membrane potential, and BCL-2 expression were determined by flow cytometry.RESULTS: Both preparations inhibited the growth of breast cancer cells in a dose-dependent- manner. Induction of apoptosis was associated with activation of caspases 3, 8 and 9, depolarization of the mitochondrial membrane potential and down-regulation of BCL-2 expression. Furthermore, A. princeps smoke exerted synergistic cytotoxicity with doxorubicin.CONCLUSION: The data suggest that A. princeps smoke and water soluble extracts induce apoptosis via the mitochondrial pathway and may represent a novel adjuvant for the treatment of breast cancer.

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