Anemonine

J Dermatol Sci. 2008 Feb;49(2):115-23.

Anemonin is a natural bioactive compound that can regulate tyrosinase-related proteins and mRNA in human melanocytes.[Pubmed: 17766092 ]

Melanin is the pigment responsible for skin color. Melanin synthesis occurs with the participation of the tyrosinase (TYR) family of proteins including TYR, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2(TRP2/DCT). The effect of a newly isolated natural compound that inhibits hyperpigmentation on the regulation of the TYR family of proteins was examined.
METHODS AND RESULTS:
The natural compound, anemonin, was isolated from Clematis crassifolia Benth and was used to inhibit cellular TYR activity; it was found to have a low cytotoxicity (cell viability > 80%) in human melanocytes. In human melanocytes, anemonin showed both time- and dose-dependent inhibition (IC(50) 43.5 microM) of TYR. Western blot analysis and immunocytochemical staining revealed that expression of TYR, TRP1, and TRP2 was decreased in anemonin-treated melanocytes. Additionally, reverse transcription and quantitative real-time polymerase chain reaction analyses revealed that expression of mRNAs for MITF, TYR, TYRP1, and TYRP2 was also suppressed by anemonin.
CONCLUSIONS:
The natural compound, anemonin, an active compound of C. crassifolia, inhibits pigmentation synthesis in human melanocytes. Anemonin inhibits melanin synthesis by inhibiting the transcription of the genes encoding MITF, TYR, TRP1, and TRP2. This natural compound may be a candidate for cosmetic use.

J Ethnopharmacol. 2008 Mar 28;116(3):518-27.

Anemonin, from Clematis crassifolia, potent and selective inducible nitric oxide synthase inhibitor[Pubmed: 18281171 ]

The aim of this study was to examine the anti-inflammatory effects of aerial part of Clematis crassifolia Benth. (Ranunculaceae) based on an iNOS inhibition in lipopolysaccharide (LPS) activated macrophages.
METHODS AND RESULTS:
Bioassay-guided fractionation and purification led to the isolation of ibotanolide B (1), calceolarioside B (2), trans-caffeic acid (3), anemonin (Anemonine,4) and 3',4',5,7-tetrahydroxy-6-C-glucopyranosylflavone (5). Their structures were elucidated on the basis of spectroscopic analysis. All these compounds inhibited NO production, detected as nitrite, in activated macrophages except 5. Among them, anemonin (Anemonine,4) was the most potent. Analyses of reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting revealed that it decreased the expression of iNOS mRNA and protein in activated RAW 264.7 cells. In isolated rat thoracic aortic rings, anemonin(Anemonine) prevented the vascular hyporeactivity to phenylephrine induced by LPS whereas it did not affect acetylcholine-induced endothelial NO-dependent relaxation, an index of endothelial NOS (eNOS) activity.
CONCLUSIONS:
These results indicated that the potential anti-inflammatory effect of anemonin(Anemonine), the naturally occurring selective iNOS inhibitor, may provide a rationale for the medical use of Clematis crassifolia.

J Mol Neurosci. 2014 Jun;53(2):271-9.

Anemonin alleviates nerve injury after cerebral ischemia and reperfusion (i/r) in rats by improving antioxidant activities and inhibiting apoptosis pathway.[Pubmed: 24443273 ]

In the present study, we aimed at evaluating the potential neuroprotective effect and the underlying mechanism of anemonin against cerebral ischemia and reperfusion (I/R) injury.
METHODS AND RESULTS:
Anemonin was administered to rats by the intraperitoneally (i.p.) route once daily for 7 days before middle cerebral artery occlusion (MCAO). Focal cerebral ischemia was induced by 90 min of MCAO followed by 24 h of reperfusion. After that, animals were sacrificed by decapitation, brain was removed, and various biochemical estimations, neurological status, and assessment of cerebral infarct size were carried out. MCAO followed by 24 h of reperfusion caused a significant increase in infarct size, neurological deficit score, malondialdehyde (MDA) content, reactive oxygen species (ROS) level, and DNA fragmentation, as well as a decrease in the activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and Na(+), K(+)-ATPase in the brain. Furthermore, elevated Bax expression, increased caspase-3 cleavage, and decreased Bcl-2 expression were observed in nontreated rats in response to focal cerebral I/R injury. However, pretreatment with anemonin significantly reversed these levels of biochemical parameters, reduced cerebral infarct size, and improved the neurologic score in cerebral ischemic animals. Additionally, a wide distribution of anemonin in plasma and brain tissues and the brain-to-plasma partition coefficient (Ri) ratio of 0.7 at 90 min indicated that this compound could penetrate the blood-brain barrier (BBB).
CONCLUSIONS:
These results showed that pretreatment with anemonin provided a significant protection against cerebral I/R injury in rats by, at least in part, its antioxidant action and consequent inhibition of apoptosis.

J Cell Mol Med. 2017 Jun 23

Anemonin attenuates osteoarthritis progression through inhibiting the activation of IL-1β/NF-κB pathway.[Pubmed: 28643466 ]

The osteoarthritis (OA) progression is now considered to be related to inflammation. Anemonin (Anemonine,ANE) is a small natural molecule extracted from various kinds of Chinese traditional herbs and has been shown to inhibiting inflammation response.
METHODS AND RESULTS:
In this study, we examined whether ANE could attenuate the progression of OA via suppression of IL-1β/NF-κB pathway activation. Destabilization of the medial meniscus (DMM) was performed in 10-week-old male C57BL/6J mice. ANE was then intra-articularly injected into joint capsule for 8 and 12 weeks. Human articular chondrocytes and cartilage explants challenged with interleukin-1β (IL-1β) were treated with ANE. We found that ANE delayed articular cartilage degeneration in vitro and in vivo. In particular, proteoglycan loss and chondrocyte hypertrophy were significantly decreased in ANE -treated mice compared with vehicle-treated mice.
CONCLUSIONS:
ANE decreased the expressions of matrix metalloproteinase-13 (MMP13), A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), collagen X (Col X) while increasing Aggrecan level in murine with DMM surgery. ANE treatment also attenuated proteoglycan loss in human cartilage explants treated with IL-1β ex vivo. ANE is a potent protective molecule for OA; it delays OA progression by suppressing ECM loss and chondrocyte hypertrophy partially by suppressing IL-1β/NF-κB pathway activation.

Pharmazie. 2016 Mar;71(3):134-8.

Skin permeation profile and anti-inflammatory effect of anemonin extracted from weilingxian.[Pubmed: 27183707]

The aim of this study was to evaluate the skin permeability of anemonin(Anemonine), which was extracted from the Chinese herb weilingxian, and its potency of relieving the inflammation caused by rheumatoid arthritis (RA).
METHODS AND RESULTS:
To optimize the formulation, the solubility of anemonin in water and selected concentration of ethanol-water vehicles was determined. The effect of ethanol on the permeation of anemonin through human skin was then studied. Additionally, the influences of hydroxypropyl methylcellulose E50 (HPMC) and Carbomer 934 in different concentrations on the permeation of drug were investigated. Finally, the anti-inflammatory effect of the optimized formulation was assessed by murine model of xylene-induced ear edema.
CONCLUSIONS:
The results showed that the solubility and transdermal permeation of anemonin(Anemonine) in ethanol-water vehicles linearly depended on the ethanol concentration. The combination of 30% ethanol and 3% Azone had a synergistic enhancement effect and was therefore selected for gel preparation. The 0.14% anemonin(Anemonine) gel prepared with 1% HPMC exhibited the highest transdermal flux. The xylene-induced ear edema inhibitory rate of the optimized formulation was 48.85%. The results indicated that transdermal administration of anemonin(Anemonine) is a potential modality for combating inflammation caused by RA.