Accessing Lipophilicity and Biomimetic Chromatography Profile of Biologically Active Ingredients of Botanicals Used in the Treatment of Inflammatory Bowel Disease

Abstract

In the present study, various procedures have been compared for the determination of lipophilicity, hydrophobicity, and plasma protein binding of curcuminoids, boswellic acids, andrographolides, and piperine as biologically active ingredients of botanicals used in IBD treatment. Our results have shown that IAM-HPLC assay is the most suitable one for lipophilicity determination of all analytes regardless of their class and botanical source. HSA-HPAC and AGP-HPAC assays revealed that all investigated compounds have a higher affinity for HSA which is the most abundant protein in human plasma. The high affinity of biologically active compounds to all biological structures (phospholipids and proteins) admonishes that their small portion is available for therapeutic effects in IBD patients. Our experimental research is complemented by various theoretical approaches based on different algorithms for pharmacokinetic properties prediction. The similarities between experimental and calculated values were evaluated using PCA and CA as a statistical tool. The statistical analysis implies that plasma protein binding is a complex process, and theoretical approaches still cannot fully replace experimental ones.

Keywords: biomimetic chromatography; botanicals; immobilized artificial membrane; inflammatory bowel diseases; plasma protein binding; shake-flask method.

Figure 1

Chemical structures of curcuminoids (curcumin (a), demetoxycurcumin (b) and bisdemetoxycurcumin (c)), boswellic acids (α-boswellic acid (d), β-boswellic acid (e), 11-keto-β-boswellic acid (f) and 3-acetyl-11-keto-β-boswellic acid (g)), andrographolides (andrographolide (h) and neoandrographolide (i)) and piperine (j).

Figure 2

Results of PCA analysis reflecting correlation between predicted and experimentally observed values.

Figure 3

Results of CA showing (a) observed dendrogram in full scale from 0–450,000 with brake after 15,000, and (b) dendrogram showing only 0–50 range of dissimilarity values.