• Applied Biological Chemistry
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• 제35권2호
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• pp.106-109
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• 1992

국화과의 일증인 개똥쑥(Artemisia annua L., 청호(靑蒿))에는 항말라리아 물질인 artemisinin이 함유되어 있다. 11,12-Dihydroarteanuic acid는 cell-free 방법으로 수행한 실험에서, Agrobacterium tumefaciens로 형질 전환된 crown gall의 homogenate와의 incubation에서 artemisinin으로 전환되었다. 그러나 arteannuic acid는 NADPH와 함께 incubation하였을 때 dihydro acid로 전환되지 않았다. 따라서 이 결과는 식물체의 조건에 따라서, dihydro acid가 자발적으로 뿐만 아니라, 생체내에서 효소 반응에 의해서도 artemisinin으로 전환될 수 있음을 나타낸다.

• 대한수의학회지
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• 제35권1호
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• pp.123-130
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• 1995

Artemisinin, a sesquiterpene lactone, is isolated from the leafy portion of the Artemisia annua and has been known to be effective against Plasmodium species. Since the genera of Plasmodium and Eimeria(E) tenella are included the same order, Eucoccidiidae, it is presumed that artemisinin may also be effective against E tenella. In order to study the anticoccididal effects of artemisinin, the chickens inoculated with E tenella were treated with artemisinin at different concentrations as feed additive and the results were compared to those of non-medicated, infected control(NIC) and non-medicated, non-infected control(NNC) group. Artemisinin demonstrated anticoccidial effects by showing, compared to NIC group, improved results in all parameters, such as bloody diarrhea, lesion scores, the numbers of excreted oocystis in feces, body weight gain and feed conversion rate. Anticoccidial index(ACI) of artemisinin treated group (5ppm~50ppm) was higher than that of NIC group. Improvements were greatest in the group treated with artemisinin 50ppm with an ACI of 147.6. These results indicate that artemisinin has anticoccidial effects on the Eimeria tenella.

• 대한의생명과학회지
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• 제29권3호
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• pp.184-189
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• 2023

Normal activation of platelets and their aggregation are crucial during hemostasis process. It appears excessive or abnormal aggregation of platelets may bring about cardiovascular diseases like stroke, atherosclerosis, and thrombosis. For this reason, finding a substance that can regulate platelet aggregation or suppress aggregation will aid in the prevention and treatment of cardiovascular diseases. Artemisinin, a compound derived from Artemisia or Scopolia plants, has shown potential in various areas such as anticancer and Alzheimer's disease research. However, the specific role and mechanisms by which artemisinin influences platelet activation and thrombus formation are not yet fully understood. This study investigated the effects of artemisinin on platelet activation and thrombus formation. This study examined the effect of artemisinin on regulation of U46619-induced platelet aggregation, granule secretion. In addition, the effects of artemisinin on phosphorylation of PI3K/Akt and MAPK pathway involved in platelet aggregation was studied. As a result, artemisinin significantly downregulated of PI3K/Akt and MAPK pathway. In addition, artemisinin significantly reduced granule secretion, and platelet aggregation was inhibited by artemisinin. Therefore, we suggest that artemisinin is an anti-platelet substance that regulates PI3K/Akt and MAPK pathway and is valuable as a therapeutic and preventive agent for platelet-derived cardiovascular disease.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.402-407
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• 2023

혈소판 응집의 조절은 정상적인 지혈을 유지하는 데 중요하지만 비정상적이거나 과도한 혈소판 응집은 뇌졸중, 죽상동맥 경화증 및 혈전증과 같은 심혈관 질환에 기여할 수 있다. 따라서 혈소판 응집을 제어하거나 억제할 수 있는 물질을 식별하는 것은 이러한 상태의 예방 및 치료를 위한 유망한 접근 방식이다. Artemisia 또는 Scopolia 속 식물에서 추출한 artemisinin은 항암 및 알츠하이머병 연구와 같은 다양한 분야에서 가능성을 보여주었다. 그러나 artemisinin이 혈소판 활성화 및 혈전 형성에 영향을 미치는 구체적인 역할과 메커니즘은 아직 완전히 밝혀지지 않았다. 이 연구는 혈소판 활성화 및 혈전 형성에 대한 artemisinin의 효과를 조사하였다. 그 결과, cAMP 생성과 cAMP 의존성 kinase에 대한 기질인 VASP 및 IP₃R의 인산화가 artemisinin에 의해 유의미하게 증가되었다. IP₃R의 인산화는 조밀한 관형 시스템에서 정상적으로 동원되는 Ca²⁺를 억제하였고, VASP의 인산화는 αIIb/β₃ 혈소판 막 불활성화를 통한 fibrinogen 결합을 억제하였다. 마지막으로, artemisinin은 thrombin이 유발하는 혈전 형성을 농도의존적으로 억제하였다. 따라서 우리는 artemisinin이 혈소판 활성화의 효과적인 예방 및 치료제로 작용하여 비정상적인 혈소판 응집 및 혈전 형성으로 인해 유발되는 심혈관 질환의 개선에 기여할 수 있음을 제안한다.

• Journal of Plant Biotechnology
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• 제49권4호
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• pp.307-315
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• 2022

개똥쑥은 말라리아 등 다양한 질병의 치료물질인 artemisinin 제공하나, 식물체 내 농도가 낮고, 생산이 불안정하여 국제적 수요에 대응하지 못하고 있다. 재배환경을 인공적으로 제어하는 식물공장 시스템은 계절이나 장소에 제한 없이 약용식물의 공장식 생산체계가 가능하다(Kim 2010). 본 연구에서는 식물공장에서 개똥쑥의 artemisinin의 대량생산이 가능한 최적의 조건을 찾기 위하여 파종부터 수확까지 적색광(R)과 청색광(B)을 혼합한 3종류의 LED (R : B = 6 : 4, 7 : 3, 8 : 2)에서 생장 및 물질생산에 적합한 광조건을 탐색하였다. 개똥쑥의 수확 전, 1,395 ㎼/cm²의 UV-B, 4℃의 저온, 그리고 건조 처리로 식물에 hormesis를 유도하여 artemisinin의 생산 증가를 확인하였다. Artemisinin 생합성에 관여하는 효소들 중에서 ADS, CYP, ALDH1의 발현량을 qPCR로 측정하였고, artemisinin 정량을 통해 전사체와 대사물질의 연관성을 확인하고, artemisinin 생산에 적합한 재배 광조건과 hormesis 처리 조건을 탐색하였다. 3종의 LED 비율 중 8 : 2에서 높은 생체중 및 건물중을 생산했으며, hormesis를 유도하기 위한 3종의 물리 처리에서 이를 통해 7 : 3 식물을 수확전 6시간 건조처리했을 때 artemisinin 함량이 약 2배 증가하였다.

• Bulletin of the Korean Chemical Society
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• 제29권7호
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• pp.1386-1390
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• 2008

Artemisinin, the effective ingredient of Chinese herb Artemisia annua L (Qinghao in Chinese), has been proved to be effective to antimalarial. Herein, a reliable, sensitive and convenient electrochemical method was developed for the determination of artemisinin utilizing the excellent properties of multi-wall carbon nanotube (MWNT). The electrochemical behavior of artemisinin was investigated. It is found that the reduction peak current of artemisinin remarkably increases and the peak potential shifts positively by 240 mV at the MWNT film-modified electrode. These phenomena indicate that the MWNT film exhibits efficient catalytic activity to the electrochemical reduction of artemisinin. The effects of pH value, amount of MWNT, scan rate and accumulation time were examined. The limit of detection (S/N = 3) is as low as 10 $\mu$ g $L^{-1}$. Finally, this newly developed method was used to determine the content of artemisinin in Artemisia annua L.

• Parasites, Hosts and Diseases
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• 제55권6호
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• pp.661-665
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• 2017

We synthesized C-10 substituted triazolyl artemisinins by the Huisgen cycloaddition reaction between dihydroartemisinins (2) and variously substituted 1, 2, 3-triazoles (8a-8h). The antimalarial activities of 32 novel artemisinin derivatives were screened against a chloroquine-resistant parasite. Among them, triazolyl artemisinins with electron-withdrawing groups showed stronger antimalarial activities than those shown by the derivatives having electron-donating groups. In particularly, m-chlorotriazolyl artemisinin (9d-12d) showed antimalarial activity equivalent to that of artemisinin and could be a strong drug candidate.

• Archives of Pharmacal Research
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• 제29권1호
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• pp.50-58
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• 2006

Translationally controlled tumor protein (TCTP), also known as histamine releasing factor (HRF), is found abundantly in different eukaryotic cell types. The sequence homology of TCTP between different species is very high, belonging to the MSS4/DSS4 superfamily of proteins. TCTP is involved in both cell growth and human late allergy reaction, as well as having a calcium binding property; however, its primary biological functions remain to be clearly elucidated. In regard to many possible functions, the TCTP of Plasmodium falciparum (Pf) is known to bind with an antimalarial agent, artemisinin, which is activated by heme. It is assumed that the endoperoxide-bridge of artemisinin is opened up by heme to form a free radical, which then eventually alkylates, probably to the Cys14 of PfTCTP. Study of the docking of artemisinin with heme, and subsequently with PfTCTP, was carried out to verify the above hypothesis on the basis of structural interactions. The three dimensional (3D) structure of PfTCTP was built by homology modeling, using the NMR structure of the TCTP of Schizosaccharomyces pombe as a template. The quality of the model was examined based on its secondary structure and biological function, as well as with the use of structure evaluating programs. The interactions between artemisinin, heme and PfTCTP were then studied using the docking program, FlexiDock. The center of the peroxide bond of artemisinin and the Fe of heme were docked within a short distance of $2.6{\AA}$, implying the strong possibility of an interaction between the two molecules, as proposed. When the activated form of artemisinin was docked on the PfTCTP, the C4-radical of the drug faced towards the sulfur of Cys14 within a distance of $2.48{\AA}$, again suggesting the possibility of alkylation having occurred. These results confirm the proposed mechanism of the antimalarial effect of artemisinin, which will provide a reliable method for establishing the mechanism of its biological activity using a molecular modeling study.

• The Korean Journal of Pain
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• 제32권3호
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• pp.160-167
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• 2019

Background: Pain is a complex mechanism which involves different systems, including the opioidergic and GABAergic systems. Due to the side effects of chemical analgesic agents, attention toward natural agents have been increased. Artemisinin is an herbal compound with widespread modern and traditional therapeutic indications, which its interaction with the GABAergic system and antinoniceptive effects on neuropathic pain have shown. Therefore, this study was designed to evaluate the antinociceptive effects of artemisinin during inflammatory pain and interaction with the GABAergic and opioidergic systems by using a writhing response test. Methods: On the whole, 198 adult male albino mice were used in 4 experiments, including 9 groups (n = 6) each with three replicates, by intraperitoneal (i.p.) administration of artemisinin (2.5, 5, and 10 mg/kg), naloxone (2 mg/kg), bicuculline (2 mg/kg), saclofen (2 mg/kg), indomethacin (5 mg/kg), and ethanol (10 mL/kg). Writhing test responses were induced by i.p. injection of 10 mL/kg of 0.6% acetic acid, and the percentage of writhing inhibition was recorded. Results: Results showed significant dose dependent anti-nociceptive effects from artemisinin which, at a 10 mg/kg dose, was statistically similar to indomethacin. Neither saclofen nor naloxone had antinociceptive effects and did not antagonize antinociceptive effects of artemisinin, whereas bicuculline significantly inhibited the antinocicptive effect of artemisinin. Conclusions: It seems that antinocicptive effects of artemisinin are mediated by $GABA_A$ receptors.

• 혜화의학회지
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• 제4권2호
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• pp.335-336
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• 1996

Artemisinin, a new antimalarial to treat patients infected with strains of Plasmodium jalciparum, derived from the plant Artemisia annua Linn, has immunopharmacologic actions such as enhence the PHA -induced lymphocyte transformation rate, increased the weight of spleen but reduced the weight of thymus, reduced phagocytic function of peritoneal macrophage, remarkably reduced the level of serum IgG and hemolysin fonning capacity (sentitized with SRBC), inhibited the activity of Ts cells of donor mice by supraoptimal immunuization(SOI), but enhenced activity of Ts cells of recipient mice by SOI. These results suggested that Ts cells may be the target cells of artemisinin. To the serum complement C3 level of plasmodium berghei-infeted mice, artemisinin (i. m,) could remarkly increase it. The artemisinin also obviously reduced the prostaglandin E(PGE) in the mouse hind paw swelling induced by carrageenin. Numerous studies have demonstrated that pharmacologic doses of PGE attenuate the development of immunocomplex nephritis. Some autologous immune mechanisms may be invoolved In the pathogensis of some types of glomurulonephritis. Glomerular abnormalities can be induced in animals by variety of immunological manipulations. The resulting disorder has many clinical and pathogical similarities to the disease in human. Our purpose was therefore to test the ability of the artemisinin to lessen the severity of rabbit IgG accelerated nephrotoxic serum glomerulonephritis in mice model. Mice which had treated with rabbit IgG and NTS, administrated with saline, showed Significant inceases of urinary protein, cholesterol level, and decrease of serum albumin in NS group. On the contrary, By i.g. adminstration of artemisinin at dose of 12.5, 25 and 50 mg/kg for 14 days after NTS injection, shown that artemisinin inhibited the nephritic changes in some parameters by means of urinary protein(p<0.05, p<0.01) and serum choleterol(p<0.05, p<0.01) and albumin (p<0.05, p<0.01), blood urea nitrogen (p<0.05, p<0.01), serum albumin(p<0.05, p<0.01); Cyclophosphamide(i.p. 10mg/kg for 14d) had almost same effect as the artemisinin had. Morphological studies shown that The picture of kidney from the mouse with NTS-nephritis accerated with rabbit IgG, treated with i.g. saline as the control, the mesangiocapillary were enlarged and proliferated; There were inflammatory cells infiltrating around the glomeruli; The ethelial cell were proliferated in the wall of Bowman's capsule. Histopatholological picture of kidney from the NTS-nephritis accerated with rabbit IgG mouse treated with i.p. 10mg/kg cyclophosphamide as the positive control. No siginicant histopathological evidence were found. Treaded with i.p. 12.5mg/kg artemisinine, the picture shown that mesangiocapillary were lightly proliferated; There were inflammatory cells infiltrating around the glomeruli; Treaded with i.p. 25mg/kg artemisinine, The picture shown that the mesangiocapillary were lightly proliferated; Treaded with i.p. 50mg/kg artemisinine, The picture shown that both the mesangiocapillary proliferated and the inflammatory cells infiltrating around the glomeruli are less than treated with saline, 12.5 and 25 mg/kg artemisinine. On the basis of these studies we conclude that the artemisinin can relieve pathological change caused by NTS-nephritis aacerated with rabbit IgG.