Author manuscript, available in PMC 2011 July 23. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript Figure 2. Withanolide A down regulates BACE1 and up regulates ADAM10. Cortical neurons were treated with 0, 5, 20 and 100 M of 1 for bcl-2 family 24 h. Immunoblots show significant downregulation in BACE1 levels and also up regulation of active ADAM10 levels in neurons treated with 1 as compared to respective controls. Histograms corresponding to BACE1 and ADAM10 blots represent quantitative determinations of intensities of the relevant bands normalized to actin. Data represent the mean S.D. of three independent experiments. The Student,s t test was used for analyzing the differences between the two treatment groups. Patil et al. Page 13 J Nat Prod. Author manuscript, available in PMC 2011 July 23.
NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript Figure 3. Asiatic acid down regulates BACE1 and up regulates ADAM10. Cortical neurons buy BIBR 1532 were treated with 0, 1, 5 and 10 M of 2 for 24 h. Immunoblots show significant down regulation in BACE1 levels as well as up regulation of mature ADAM10 levels in neurons treated with 2 as compared to respective controls. Histograms corresponding to BACE1 and ADAM10 blots represent quantitative determinations of intensities of the relevant bands normalized to actin. Data represent the mean S.D. of three independent experiments. The Student,s t test was used for analyzing the differences between the two treatment groups. Patil et al. Page 14 J Nat Prod. Author manuscript, available in PMC 2011 July 23.
NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript Figure 4. Effects of 1 and 2 on APP processing. Immunoblots show a dose dependent increase in the levels of C83 and sAPP in neurons treated with 1 and 2 as compared to their respective controls. Histograms corresponding to sAPP blot represent quantitative determinations of intensities of the relevant bands normalized to actin. Data represent mean S.D. of three independent experiments. The Student,s t test was used for analyzing the differences between the two treatment groups. Patil et al. Page 15 J Nat Prod. Author manuscript, available in PMC 2011 July 23. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript Figure 5. Dose dependent effects of withanolide A on targets involved in A degradation.
Cortical neurons were treated with 0, 5, 20 and 100 M of 1 for 24 h. Immunoblots show significant up regulation of IDE, while NEP remained unaffected, in neurons treated with 1 in a dose dependent manner as compared to controls. Histograms corresponding to IDE and NEP blots represent quantitative determinations of intensities of the relevant bands normalized to actin. Data represent mean S.D. of three independent experiments. The Student,s t test was used for analyzing the differences between the two treatment groups. Patil et al. Page 16 J Nat Prod. Author manuscript, available in PMC 2011 July 23. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript Asiatic Acid, a Pentacyclic Triterpene From Centella asiatica, Is Neuroprotective in a Mouse Model of Focal Cerebral Ischemia Rajanikant G.
Krishnamurthy1, Marie Claude Senut1, Daniel Zemke1, Jiangyong Min1, Mark B. Frenkel1, Eric J. Greenberg1, Seong Woon Yu1,2, Nick Ahn1,2, John Goudreau1,2, Mounzer Kassab1, Kiran S. Panickar3, and Arshad Majid1, 1Division of Cerebrovascular Diseases and Department of Neurology and Ophthalmology, Michigan State University, East Lansing, Michigan 2Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 3Diet, Genomics, and Immunology Laboratory, United States Department of Agriculture, Beltsville, Maryland Abstract Asiatic acid, a triterpenoid d