| Summary: | 博士 === 臺北醫學大學 === 藥學系 === 94 === Heightened oxidative stress is an important mechanism in the pathogenesis of liver diseases caused by exposure to environmental toxins. Herbal supplements and Chinese medicine may contain ingredients that are protective against oxygen free radical-induced liver damage. In the present study, we discovered (1) Ge-Gen Huang –Lian Huang-Qin (GHH) Decoction, prescribed in traditional Chinese medicine for treating liver diseases, suppressed hepatic lipid peroxidation (LPO); (2) selected flavonoids (flavones, flavonols, flavanones and flavanonols) derived from GHH and other sources bear a quantitative structure activity relationship (QSAR) that fitted a model with the following equation:
Y = 0.92X1－0.35X2－0.000051X3－0.0046X4－0.21X5＋3.26, r2=0.95, r2cv =0.93
(Y denotes antioxidant potency; a value of 1 is assigned to X1 if a functional group is present at both positions 5 and 8 of ring A in the flavonoid structure and X2, for positions 3’ and 4’ in ring B; X3, HOMO energy; X4, electrostatic energy; X5, bond energy; r2, linear regression coefficient; r2cv, cross validation coefficient)
This equation predicted that the protective effects of flavones were more potent than flavonols, flavanones or flavanonols in tert-butyl hydroperoxide-induced LPO. QSAR studies indicate that the energy parameters are important factors in predicting the potency of flavones, flavonols, flavanones and flavanonols in suppressing LPO in liver. The same equation also applies to flavones from herbs not contained in GHH (e.g., morusin, cyclomuberrin, cyclomuberrochromene and others derived from Morus abla); and (3) combination of GHH and Morus abla conferred a greater effect in suppressing hepatic LPO.
Adverse side effects may develop when Chinese medicine is administered along with prescription drugs. It is important to assess potential interaction of these 2 groups of medications. We noted in the present study that baicalein and daidzein, 2 flavonoids derived from GHH reduced the WAR binding levels by 9% and 21%, respectively. Berberine, also a GHH ingredient, reduced ibuprofen (IBU) binding to human serum albumin (HSA) by 81%. It also altered disopyramide (DIP) binding to α1-acid glycoprotein (AGP) by 73%. Glycyrrhizic acid, another GHH ingredient, reduced IBU binding to HSA by 28% and salicylic acid (SAL) binding by 42%. To further verify the clinical significance of the effects of Chinese medicine on drug binding to serum proteins. Siwu decoction, the most commonly prescribed herbal medicine, also examined for its effects on SAL, one of the most frequently prescribed medications, binding to HSA. Siwu decoction increased serum free SAL by 37%. These results suggest that various herbal formulae are likely to alter free drug levels, affecting their efficacy or causing unexpected side effects.
In summary, we found that GHH was an effective regimen for reducing LPO in liver. The model was useful in predicting the potencies of flavones, major flavonoid gradients in GHH, in reducing liver LPO. Combination of GHH and Morus alba conferred a greater protective potency against LPO. However, flavonoids in GHH, such as baicalein and daidzein may alter drug binding to HSA, increasing or decreasing free drug levels. Co-administration of GHH with prescription drugs such as IBU, WAR and DIP should be made with caution. Results derived from the present study would be values in improving current and in developing new herb formulae.
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