| Description: |
Skimmianine is a new inhibitor against the Leishmania APRT enzyme, it is also a strong acetylcholinesterase (AChE) inhibitor. Skimmianine has anti-inflammatory, immunomodulatory, and leishmanicidal properties, it has a selective inhibitory effect on the 5-hydroxytryptamine-induced vasopressor responses of rats. |
| Targets: |
IL Receptor | NO | NOS | TNF-α | PGE | COX | LOX | SOD | AChR | 5-HT Receptor |
| In vitro: |
| Planta Med. 2011 Sep;77(14):1644-7. | | A new quinoline epoxide from the Australian plant Drummondita calida.[Pubmed: 21472648] |
METHODS AND RESULTS:
A drug discovery program aimed at identifying new antimalarial leads from a prefractionated natural product library has resulted in the purification of a new quinoline alkaloid, (2' R)-2',3'-epoxy- N-methylatanine (1), along with eight known natural products, Skimmianin, γ-fagarine, maculosidine, evolitrine, dictamnine, pteleine, N-methylatanine, and werneria chromene.
CONCLUSIONS:
Compound 1 displayed 74 % inhibition at 80 µM against a chloroquine -resistant Plasmodium falciparum strain (Dd2). | | Parasitology. 2011 Sep;138(10):1224-33. | | Leishmanicidal effect of Spiranthera odoratíssima (Rutaceae) and its isolated alkaloid skimmianine occurs by a nitric oxide dependent mechanism.[Pubmed: 21810308 ] | Leishmaniasis is one of the neglected diseases. High cost, systemic toxicity, and diminished efficacy due to development of resistance by the parasites has a negative impact on the current treatment options. Thus, the search for a new, effective and safer anti-leishmanial drug becomes of paramount importance. Compounds derived from natural products may be a better and cheaper source in this regard. This study evaluated the in vitro anti-leishmanial activity of Spiranthera odoratíssima (Rutaceae) fractions and isolated compounds, using promastigote and amastigote forms of different Leishmania species.
METHODS AND RESULTS:
J774 A.1 macrophage was used as the parasite host cell for the in vitro assays. Evaluations of cytoxicity, nitric oxide (NO), interleukin-10 and in silico analysis were carried out. In vitro experiments showed that the fruit hexanic fraction (Fhf) and its alkaloid skimmianine (Skm) have a significant (P<0·001) effect against L. braziliensis. This anti-L. braziliensis activity of Fhf and Skm was due to increased production of NO and attenuation of IL-10 production in the macrophages at concentrations ranging from 1·6 to 40·0 μg/ml.
CONCLUSIONS:
The in silico assay demonstrated significant interaction between Skm and amino acid residues of NOS2. Skm is thus a promising drug candidate for L. braziliensis due to its potent immunomodulatory activity. |
|
| In vivo: |
| Inflamm Res. 2013 Apr;62(4):367-76. | | Anti-inflammatory effect of quinoline alkaloid skimmianine isolated from Ruta graveolens L.[Pubmed: 23344232 ] | The present study evaluates the anti-inflammatory effect of the quinoline alkaloid Skimmianine (Skimmianin,SKM), isolated from Ruta graveolens L., against carrageenan-induced acute inflammation.
METHODS AND RESULTS:
SKM at a dose of 5.0 mg/kg body weight was found to be the minimal concentration for maximal edema inhibition. Carrageenan suspension was administered into the sub-plantar tissue of the right hind paw 1 h after SKM and diclofenac (20 mg/kg) administration (i.p.). Paw edema was determined 3 h after carrageenan administration. The rats were then killed and mRNA expressions of TNF-α and IL-6, levels of PGE2 and TBARS, activities of COX-2, 5-LOX, SOD, catalase, glutathione peroxidase (GPx) and myeloperoxidase (MPO) and the level of nitrite were measured. SKM treatment resulted in a decrease in the mRNA levels of TNF-α and IL-6, which are upstream events of the inflammatory cascade. The levels of PGE2 and NO and the activities of COX-2 and 5-LOX were also significantly reduced after SKM treatment. Neutrophil infiltration, lipid peroxidation and associated oxidative stress in the paw tissue were reduced following SKM treatment.
CONCLUSIONS:
These results support the anti-inflammatory properties of Skimmianine and its multi-targeted mechanism of action, suggesting its potential therapeutic efficacy in various inflammatory diseases. |
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