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Abstract
BackgroundIridoid glycosides (IGs), including monotropein (MON) and deacetyl asperulosidic acid (DA) as the main ingredients, are the major chemical components in Morinda officinalis How. (MO) root, possessing various pharmacological properties including anti-osteoporosis, anti-inflammation and anti-rheumatism activities.The aim of the present study was to further elucidate the pharmacological actions of MO by investigating the pharmacokinetics and tissue distribution of IGs in MO.MethodsAn ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) method was developed and validated for simultaneous determination of MON and DA levels in plasma and various tissues of Wistar rats. MON, DA and acetaminophen (ACE) as the internal standard (IS) were extracted from rat plasma and tissue samples by direct deproteinization with methanol. The rats were administered orally at 1650 mg/kg MO and 25, 50 and 100 mg/kg MO iridoid glycosides (MOIGs) or intravenously at MOIG 25 mg/kg for pharmacokinetic study of MON and DA. In addition, 100 mg/kg MOIG was administered orally for tissue distribution study of MON and DA. Non-compartmental pharmacokinetic profiles were constructed. Tissue distributions were calculated according to the validated methods.ResultsSignificant differences in the pharmacokinetic parameters were observed in male and female rats. The AUC0-t, Cmax and bioavailability of MON and DA in female rats were higher than those in male rats. MON and DA mainly distributed in the intestine and stomach after oral administration, and noteworthily high concentrations of MON and DA were detected in the rat hypothalamus.ConclusionThe results of the present study may shed new lights on the biological behavior of MOIGs in vivo, help explain their pharmacological actions, and provide experimental clues for rational clinical use of these IGs extracted from the MO root.
Highlights
Iridoid glycosides (IGs), including monotropein (MON) and deacetyl asperulosidic acid (DA) as the main ingredients, are the major chemical components in Morinda officinalis How. (MO) root, possessing various pharmacological properties including anti-osteoporosis, anti-inflammation and anti-rheumatism activities.The aim of the present study was to further elucidate the pharmacological actions of MO by investigating the pharmacokinetics and tissue distribution of IGs in MO
The present study showed that the pharmacokinetic parameters for male and female rats were significantly different
Our experiments indicated that MO iridoid glycosides (MOIGs) at dose of 22.5 g/kg did not cause any death of mice
Summary
Iridoid glycosides (IGs), including monotropein (MON) and deacetyl asperulosidic acid (DA) as the main ingredients, are the major chemical components in Morinda officinalis How. (MO) root, possessing various pharmacological properties including anti-osteoporosis, anti-inflammation and anti-rheumatism activities.The aim of the present study was to further elucidate the pharmacological actions of MO by investigating the pharmacokinetics and tissue distribution of IGs in MO. The root of Morinda officinalis How (MO), named as “Bajitian” in traditional Chinese medicine [1], has long been used as a tonic or nutrient supplement to prevent and treat multiple diseases including osteoporosis, depression, rheumatoid arthritis, impotence and Alzheimer disease in China, South Korea, Japan and Southeast Asia [2,3,4,5,6] These pharmacological properties are believed to be mainly attributed to oligosaccharides, polysaccharides, iridoid glucosides, antharaquinines and volatile oil as the main chemical constituents in the MO root [7,8,9]. In our previous work on chemical compounds of the MO root [13], we extracted MOIGs from the MO root by using an optimal technical method and found that content of MON and DA was greater than 60%, suggesting potential therapeutic applications of MOIGs in the treatment of inflammatory and bone diseases such as osteoarthritis, rheumatoid arthritis and inflammatory bone loss
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