Novel Bile Acids from Bear Bile Powder and Bile of Geese

Abstract

Bile acids, as the water-soluble amphipathic end products of cholesterol metabolism, are important due to their roles in elimination of cholesterol and absorption of lipids and fatsoluble vitamins in the intestine.1) C24 bile acids found in most mammals are present in bile as N-acyl amidates (conjugates) of taurine or glycine.2) All primary C24 bile acids have a hydroxyl group at C-3 which is from cholesterol and at C-7, as cholesterol 7a-hydroxylation is the rate-limiting step in bile acid biosynthesis. Thus, chenodeoxycholic acid (CDCA; 3a,7a-dihydroxy-5b-cholan-24-oic acid) is the root C24 bile acid.3) Chenodeoxycholic acid and ursodeoxycholic acid (UDCA; 3a,7a-dihydroxy-5b-cholanoic acid) are widely used for the treatment of cholesterol gall-stones and ursodeoxycholic acid has been introduced for the therapy of cholestatic liver diseases. [4][5][6][7][8][9] In the previous study, several bile acids including CDCA, CA, TCDCA, TUDCA, TCA were obtained from bile of Ursus arctos by Yamaguchi et al. 10) In order to search for new natural bioactive constituents from animal bile and provide chemical standards for the research on its quality control, two kinds of bile from different animals including Selenaretos thibetanus CUVIER and Anser anser domesticus were chemically investigated in our research group. This paper describes the isolation and structural determination of two novel bile acids, tauroselocholic acid (1), tauroansocholic acid (2), and a new natural bile acid, cygnocholic acid (3) which had been synthesized by Iida et al.,11) together with seven known compounds from these two kinds of bile. Results and DiscussionCompound 1 was isolated as colorless syrup, and it showed positive Gregory Pascoe reaction, suggesting it to be a bile acid. Its molecular formula C 26 H 45 NO 7 S was established by the pseudo-molecular ion peak at m/z 514.2860 [MϪH] Ϫ in the HR-ESI-MS and confirmed by the NMR data analysis. The IR spectrum indicated the presence of hydroxyl group (3420 cm C-NMR spectra (distortionless enhancement by polarization transfer (DEPT)) exhibited three methyls, twelve methylenes, seven methines and four quaternary carbons. Analysis of the 13 C-NMR spectrum showed three hydroxylated carbons at d 68.2 (CH), 73.1 (CH) and 75.8 (q C), and one amide carbonyl at d 176.6. The above data showed high similarity with those of the known compound, 3a,7a-dihydroxy-5b-cholanoic acid N- [2-sulfoethyl] amide (8) 10) except for an additional hydroxyl group, which implied 1 to has 3a-hydroxyl and 7a-hydroxyl substituents. Interpretation of the 1 H-1 H correlation spectroscopy (COSY) spectrum led to the determination of partial structures I, II and III (Fig. 2). Partial structure I were connected to II by heteronuclear multiple bonding connectivity (HMBC) correlations (Fig. 2) from H 3 -19 to C-5, C-9, C-10, from H 3 -18 to C-12, C-13, C-14, C-17, and from H-11b to C-8. The structural moiety I was also connected to III by HMBC correlations (Fig. 2) from H 2 -23 and H 2 -25 to C-24. Analysis of 13 C-NMR spectra t...

Differentiation of various traditional Chinese medicines derived from animal bile and gallstone: Simultaneous determination of bile acids by liquid chromatography coupled with triple quadrupole mass spectrometry

“…Snake bile, however, contained TCA as the predominant constituent. Some of these results were in accordance with previous reports [5]. These characteristics could be used as chemical markers to identify bear bile, pig bile, and snake bile.…”

“…They play an important role in lipid absorption and cholesterol catabolism, and may be promising therapeutic agents to increase the intestine absorption of vitamins, to correct biliary cholesterol saturation, and to treat cholesterol gallstones and cholestatic liver diseases [1,4,5]. Ursodeoxycholic acid (UDCA) has been approved by Food and Drug Administration for clinical use of gallstone dissolution and prevention [6].…”

Evolutionary diversity of bile salts in reptiles and mammals, including analysis of ancient human and extinct giant ground sloth coprolites

“…We examined 18 species of marsupials, which revealed uncommon bile acids relative to placental mammals and other vertebrates: 1α-hydroxy-CDCA (1α,3α,7α-trihydroxy-5β-cholan-24-oic acid) in the spotted cuscus ( Phalanger maculatus ), 1β-hydroxy-CDCA (1β,3α,7α-trihydroxy-5β-cholan-24-oic acid) in the feather-tailed glider ( Acrobates pygmaeus ), 3α-hydroxy-7-oxo-5β-cholan-24-oic acid in the Queensland koala ( Phascolarctos adjustus ), 7-oxo-DCA (3α,12α-dihydroxy-7-oxo-5β-cholan-24-oic acid) in both the kowari ( Dasyuroides byrnei ) and spotted-tailed quoll ( Dasyrus maculatus maculatus ), and 15α-hydroxy bile acids in the common wombat ( Vombatus ursinus ) [29]. Some of these substitutions have also been described in birds, e.g., 1β-bile acids in the tinamou [30], fruit pigeons, and doves [31]; and 15α-hydroxy bile acids in swans, ducks, and geese [32,33]. …”

“…The only other mammals in our survey to have more than trace amounts of ursodeoxycholic acid were several rodents, including the North American beaver ( Castor canadensis , Castoridae) and three caviomorph species within two families (Dasyproctidae, Caviidae) (Additional File 2). Recently published work by other investigators have identified two additional novel bile acids in the Asian black bear ( Selenaretos thibetanus ): 3α,5,7α-trihydroxy-5β-cholan-24-oic acid and 3α,7α,9α-trihydroxy-5β-cholan-24-oic acid [32]. …”

Chemical Synthesis of Uncommon Natural Bile Acids: The 9α-Hydroxy Derivatives of Chenodeoxycholic and Lithocholic Acids

“…Other sites of additional nuclear hydroxylation in bile acids are at C-1 (1α-/1β-), C-2 (2β-), C-4 (4β-), C-5 (5β-), and C-15 (15α-). [1][2][3] Recently, a new natural bile acid having a hydroxylation site at C-9 (9α-) in the 5β-steroid nucleus (cis A/B-ring juncture) was reported by Bi et al,5) to be present in the bile of the Asian black bear (Ursus thibetanus). The semitrivial name, selocholic acid, was proposed for this novel bile acid.…”