pseudoberberine and Hypercholesterolemia

pseudoberberine has been researched along with Hypercholesterolemia* in 2 studies

Other Studies

2 other study(ies) available for pseudoberberine and Hypercholesterolemia

Article	Year
Berberine analogues as a novel class of the low-density-lipoprotein receptor up-regulators: synthesis, structure-activity relationships, and cholesterol-lowering efficacy. Journal of medicinal chemistry, 2009, Jan-22, Volume: 52, Issue:2 Twenty-nine derivatives of berberine (1) or pseudoberberine (2) were designed, semisynthesized, and evaluated for their up-regulatory activity on the low-density-lipoprotein receptor (LDLR) expression. SAR analysis revealed that (i) the methylenedioxy group at the 2- and 3-position is an essential element to keep the activity, (ii) the 7-position quaternary ammonium and planar structure of the compound are activity-required, and (iii) addition of electron-donating groups at the 7- or 13-position reduced the activity. Of the compound 1 analogues, compound 2 exhibited an increased activity on LDLR expression compared to 1. In the hyperlipidemic rats, compound 2 (100 (mg/kg)/day) reduced blood CHO and LDL-c by 42.6% and 49.4%, respectively, more efficient than 1 did (p < 0.01 for both). The results were confirmed in the hyperlipidemic mice. LD(50) of 2 in mice was over 5000 mg/kg (oral). We consider compound 2 a promising cholesterol-lowering drug candidate. Topics: Animals; Berberine; Cholesterol; Hepatocytes; Humans; Hypercholesterolemia; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Mice; Mice, Inbred C57BL; Models, Molecular; Rats; Receptors, LDL; RNA, Messenger; Structure-Activity Relationship; Up-Regulation	2009
Synthesis and structure-activity relationships of berberine analogues as a novel class of low-density-lipoprotein receptor up-regulators. Bioorganic & medicinal chemistry letters, 2008, Aug-15, Volume: 18, Issue:16 Berberine (BBR, 1) is a novel cholesterol-lowering agent that up-regulates low-density-lipoprotein receptor (LDLR) expression through a mechanism different from that of statins. Because of the unique mode of action and good safety record, BBR provoked our interest to do structure modification at different domains for its cholesterol-lowering activity. Nineteen BBR analogues with substituents on the benzene ring D were synthesized in the present study. The analysis of structure-activity relationship (SAR) indicated that the two methoxyl groups in an ortho-distribution on this benzene ring afforded a good activity. Among the 19 analogues, compound 8j bearing a methoxyl at both 10- and 11-position showed an increased LDLR up-regulatory activity in respect to BBR, and therefore has been selected as a promising cholesterol-lowering drug candidate for further evaluation. Topics: Benzene; Berberine; Chemistry, Pharmaceutical; Drug Design; Humans; Hypercholesterolemia; Ions; Lipids; Models, Chemical; Receptors, LDL; RNA Stability; Static Electricity; Structure-Activity Relationship; Up-Regulation	2008

Article

Year

Berberine analogues as a novel class of the low-density-lipoprotein receptor up-regulators: synthesis, structure-activity relationships, and cholesterol-lowering efficacy.

Journal of medicinal chemistry, 2009, Jan-22, Volume: 52, Issue:2

Twenty-nine derivatives of berberine (1) or pseudoberberine (2) were designed, semisynthesized, and evaluated for their up-regulatory activity on the low-density-lipoprotein receptor (LDLR) expression. SAR analysis revealed that (i) the methylenedioxy group at the 2- and 3-position is an essential element to keep the activity, (ii) the 7-position quaternary ammonium and planar structure of the compound are activity-required, and (iii) addition of electron-donating groups at the 7- or 13-position reduced the activity. Of the compound 1 analogues, compound 2 exhibited an increased activity on LDLR expression compared to 1. In the hyperlipidemic rats, compound 2 (100 (mg/kg)/day) reduced blood CHO and LDL-c by 42.6% and 49.4%, respectively, more efficient than 1 did (p < 0.01 for both). The results were confirmed in the hyperlipidemic mice. LD(50) of 2 in mice was over 5000 mg/kg (oral). We consider compound 2 a promising cholesterol-lowering drug candidate.

Topics: Animals; Berberine; Cholesterol; Hepatocytes; Humans; Hypercholesterolemia; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Mice; Mice, Inbred C57BL; Models, Molecular; Rats; Receptors, LDL; RNA, Messenger; Structure-Activity Relationship; Up-Regulation

2009

Synthesis and structure-activity relationships of berberine analogues as a novel class of low-density-lipoprotein receptor up-regulators.

Bioorganic & medicinal chemistry letters, 2008, Aug-15, Volume: 18, Issue:16

Berberine (BBR, 1) is a novel cholesterol-lowering agent that up-regulates low-density-lipoprotein receptor (LDLR) expression through a mechanism different from that of statins. Because of the unique mode of action and good safety record, BBR provoked our interest to do structure modification at different domains for its cholesterol-lowering activity. Nineteen BBR analogues with substituents on the benzene ring D were synthesized in the present study. The analysis of structure-activity relationship (SAR) indicated that the two methoxyl groups in an ortho-distribution on this benzene ring afforded a good activity. Among the 19 analogues, compound 8j bearing a methoxyl at both 10- and 11-position showed an increased LDLR up-regulatory activity in respect to BBR, and therefore has been selected as a promising cholesterol-lowering drug candidate for further evaluation.

Topics: Benzene; Berberine; Chemistry, Pharmaceutical; Drug Design; Humans; Hypercholesterolemia; Ions; Lipids; Models, Chemical; Receptors, LDL; RNA Stability; Static Electricity; Structure-Activity Relationship; Up-Regulation

2008