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23 avril 2011 6 23 /04 /avril /2011 08:26

Osthole is an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, a Chinese herbal medicine, which has been used to treat anti-inflammation, anti-osteoporosis and anti-tumor for many years.

Osthol may increase androgen, gonadotropin and nitric oxide synthase (NOS) activity.

One mouse study indicates osthol had androgen like effect and gonadotropin like effect.

Little research has been done with osthole, however it appears that this substance may have a role to play in liver health, brain function, and vasodilation.

Recently, researchers from Medical School of Soochow 
University, China, found that 4-week-supplementation of osthole could inhibit alcohol or high fat-induced fatty liver in mice, probably associated with its anti-oxidation and suppression of TNF-alpha production. [1-4]

Anti-inflammatory Action

Researchers from Gannan Medical College, China, found that osthole suppressed inflammatory responses on nitric oxide levels in a dose-dependent manner in a study of rats. 
The mechanism is related to inhibition of calcium entry and elevating cGMP levels way. [5]

Osthole may benefit people suffered from some chronic conditions.

Osthole exhibited a significant induction of differentiation in two human osteoblast-like cell lines-MG-63 and hFOB. Researchers from Chia-Nan University of Pharmacy and Science, Taiwan, claimed that osthole may benefit people suffered from osteoporosis. [6] In a study of 
ovariectomized rats, osthole was as effective as 17beta-estradiol to suppress bone loss  due to ovariectomy but the researchers were not sure how osthole suppress bone loss. [8]

Because of its unique structure, the location of a butenyl group at position-8, researchers  from Nippon Chemiphar Co., Ltd, believe s osthole is a good candidate l for liver cancer (hepatocellular carcinomas) [7]

Osthole may benefit people at risk of hypertension.

Osthole causes hypotension in vivo or lowers the blood pressure of animals, and inhibits platelet aggregation and smooth muscle contraction in vitro. Researchers noted that the mechanism might work via interfering the calcium influx and cyclic nucleotide phosphodiesterases. [9]

In 1991, osthole was already known as antiplatelet agent. Thirty min after
intraperitoneal (i.p.) administration of osthole, tail bleeding time of mice was prolonged markedly in a dose-dependent manner. [13]

Researchers from National Taiwan University noticed osthole inhibited norepinephrine -induced phasic and tonic contractions in rat thoracic aorta in a concentration-dependent manner. They further found that osthole relaxed rat thoracic aorta by virtue of its Ca(2+)-channel blocking properties and by elevating cGMP levels in vascular smooth muscle. [10]

This research group also found that osthole suppressed the contraction response curves of tracheal smooth muscle of guinea-pig caused by carbachol, calcium chloride or other agents in a concentration-dependent manner.

Again, osthole inhibited the activity of cAMP and cGMP phosphodiesterases in a concentration-dependent manner. They concluded that osthole exerts a non-specific relaxant effect on the trachealis by inhibiting the cAMP and cGMP phosphodiesterases. [11]

Researchers from Xian Medical University confirmed their findings by comparing the effects of osthole and verapamil on the isolated guinea-pig ileum and taeniae coli. Both inhibited the contractions induced by acetylcholine (ACh), histamine (His) and KCl in a dose-dependent manner. [12]

Other Benefits

Osthole benefit for fatty liver
Osthole improves fat milk-induced fatty liver in rats: modulation of hepatic PPAR-alpha/gamma-mediated lipogenic gene expression.
Planta Med. 2007 July.

Department of Pharmacology, Medical School of Soochow University, Suzhou, PR China.
The objectives of this study were to determine the therapeutic effect of osthole, an active constituent isolated from Cnidium monnieri (L.) Cusson (Apiaceae), in hyperlipidemic fatty liver rats and investigate the possible mechanism of the osthole treatment. Osthole exerts therapeutic effects on fat milk-induced fatty liver in rats, by regulating mRNA expression of the target genes of CYP7A, DGAT, L-FABP and FATP4 via increasing the PPARalpha/gamma mRNA expression.

Liver cancer
Chemical aspects of coumarin compounds for the prevention of hepatocellular carcinomas.
Curr Med Chem Anti-Canc Agents. 2005. 
The normalization of plasma alanine aminotransferase (ALT) has been proved to be a strategy for preventing the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infection. Glycyrrhizin, a plant medicine, normalizes plasma ALT and prevents HCC. However, glycyrrhizin is administered intravenously and thereby chemical which is effective on oral administration is required. Coumarin compounds are active components of herbs used for the treatment of various diseases. The ability of coumarin compounds to lower plasma ALT were examined using mice concanavalin A-induced hepatitis and mice anti-Fas antibody-induced hepatitis.We conclude that osthole will become a leading chemical for synthesizing a compound which prevents liver cancer on oral administration.

Osthole mental effects
Osthole improves aspects of spatial performance in ovariectomized rats.
Am J Chin Med. 2004. 
The present study was designed to investigate the ameliorating effects of Cnidiuim monnieri L. Cusson (CM) and osthole, a constituent of cnidium, on the spatial performance deficit in scopolamine (SCOP)-treated or ovariectomized rats. Osthole improved the performance deficit in ovariectomized rats. The action mechanism of the effects of osthole on performance deficits was related to the estrogen-like properties and activating the central cholinergic neuronal system.

Osthole relaxes trachea
The relaxant action of osthole isolated from Angelica pubescens in guinea-pig trachea.
Naunyn Schmiedebergs Arch Pharmacol. 1994 Feb;349(2):202-8. 
The effect of osthole, isolated from Angelica pubescens, on the contraction of guinea-pig trachea was studied. Osthole, theophylline and higher concentrations of nifedipine suppressed the contraction response curves of tracheal smooth muscle caused by carbachol, prostaglandin F2 alpha (PGF2 alpha), U46619 (thromboxane A2 analogue) and leukotriene C4 (LTC4) in a concentration-dependent manner. It is concluded that osthole exerts a non-specific relaxant effect on the trachealis by inhibiting the cAMP and cGMP phosphodiesterases.

Plants that contain osthole A number of herbs contain osthole, including cnidium and angelica pubescens root.

      Pharmazie. 2004 Aug;59(8):643-5.

Coumarins from Cnidium monnieri (L.) and their proliferation stimulating activity on osteoblast-like UMR106 cells.

Source

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P.R. China.

The proliferation of various fractions of alcoholic extracts from fruits of Cnidium monnieri (L.) Cuss (umbelifera) were screened using the osteoblast-like UMR106 cells in vitro.

The chloroform fraction from the crude extract was found to have the most stimulating activity.

Three coumarins (osthole, bergapten and imperatorin) were isolated from this fraction by activity-guided assay, and their effects on osteoblastic proliferation were investigated.

Osthole, a major pharmacologically active constituent, significantly promoted the cells' activity.

Bergapten and imperatorin were less effective than osthole.

These results suggested Cnidium monnieri (L.) Cuss extracts might havepotential activity against osteoporosis, and its chloroform fraction might contain active constituents stimulating osteoblasts.

PMID:
 
15378857
 
[PubMed - indexed for MEDLINE]


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