Another compound worthy of potential enhancement: Baicalin
Baicalin, an emerging multi-therapeutic agent: pharmacodynamics, pharmacokinetics, and considerations from drug development perspectives.
Abstract
Baicalin was extensively researched for utility in a number of therapeutic areas owing to its anti-inflammatory, anti-oxidant, anti-bacterial, and anti-cancer properties. A number of preclinical studies, in vitro work, and mechanistic studies were performed to understand the absorption, distribution, metabolism, and excretion profiles of baicalin. The absorption of baicalin involved several complexities: the restriction to two distant sites; the conversion of baicalin to baicalein; the possible role of transporter(s); and enhanced absorption due to breakdown of conjugates by beta-glucuronidase. Limited distribution data suggest that baicalin reached several sites such as the brain, eye lens, thymus, etc. Hepatobiliary recycling also served as a distribution phase for sustained delivery of baicalin. Metabolism data suggest the rapid conversion of baicalin to baicalein, which was extensively subjected to Phase 2 metabolism, conjugates baicalein glucuronide/sulfate have been identified. Limited excretion data suggest involvement of renal and faecal routes--glucuronide and sulfate conjugates were excreted in urine and faeces (via biliary excretion). The published data on baicalin suggest imminent challenges for developing baicalin and/or during co-administration with other agents. These challenges are absorption related (transporter or changes in the microenvironment), metabolism related (CYP2B6 induction and/or CYP2E1 inhibition), and excretion/efflux related (competitive biliary pathway and/or OATP1B1 transport).
http://www.ncbi.nlm....pubmed/20230189
Enhancing effects of absorption enhancers on in situ nasal absorption of baicalin
HUANG Hui-feng,ZHANG Miao,TANG Xing(School of pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)
Objective To investigate the nasal absorption of baicalin and the enhancing activities of several absorption enhancers.Methods Nasal circulatory perfusion test in situ was employed to investigate the effects of absorption enhancers for nasal mucosa absorption of baicalin in rats.And the enchancing activities were evaluated by first-order nasal absorption rate constant k.Results Absorption enhancers were necessary to facilitate baicalin absorption by nasal mucosa.Among the absorption enhancers,the order of increasing absorption of baicalin caused by the enhancers was:1% sodium deoxycholate 0.5% chitosan≈0.5% borneol≈5% methyl-β-cyclodextrin5% HP-βCD5% β-CD1% Tween-80≈0.1% EDTA-Na2≈1% lecithin.Conclusions 0.5% chitosan,0.5% borneol,5% methyl-β-cyclodextrin and 5% HP-β-CD are the promising candidates with good enhancing activities for nasal baicalin delivery.
http://en.cnki.com.c...YD200805002.htm
Anti-bacterial Synergistic Effects of Baicalin and Borneol on Staphylococcus epidermidis
YU Yue1,WANG Ya-jing1,PI Jia-xin1,WANG Dong-heng2,XUAN Xiao-yu1,ZHENG Yin1(1.Tianjin University of Traditional Chinese Medicine,Tianjin State Key Laboratory of Modern Chinese Medicine,Tianjin 300193,China;2.Tianjin Zhongyi Pharmaceutical Co.Ltd.,Tianjin 300193,China)
Objective: The aim of this paper is to estimate the anti-bacterial effects of baicalin and borneol on Staphylococcus epidermidis.Method: A modified turbidimetry,which referred to the solution absorbance assay at 600 nm,was applied to determine the inhibition ratio of S.epidermidis growth by adding different concentrations of baicalin,borneol and baicalin-borneol mixed solutions.Result: The inhibition ratios of S.epidermidis growth of different baicalin concentration solutions with borneol added showed significant increase compared with blank baicalin solutions.The inhibition ratios were 49.78% with 1 200 mg.L-1 baicalin solution,and 13.41% with 600 mg.L-1borneol solution,separately.The significant inhibition ratio which indicated the synergistic effect was 78.15% under the mixed solution with the baicalin concentration of 1200 mg.L-1 and borneol 600 mg.L-1.Conclusion: The compatibility of a certain amount of baicalin and borneol,which significantly enhanced the anti-bacterial effects of two compounds separately,indicated the outstanding synergistic effect on the inhibition of S.epidermidis growth.
http://en.cnki.com.c...FX201310056.htm
Side note: Baicalin when used alone can actually decrease BBB permeability in certain conditions
Baicalin attenuates brain edema in a rat model of intracerebral hemorrhage.
Abstract
Baicalin is a flavonoid compound purified from the roots of Scutellaria baicalensis, which possesses multiple biological activities. Previous studies have shown that baicalin is protective in ischemic cerebral diseases. The aim of the present study was to examine the effects of baicalin on braininjury in a rat model of intracerebral hemorrhage (ICH) and to explore the possible mechanisms. Intracerebral hemorrhage was induced in male Wistar rats by injection of 0.5 U collagenaseVII to the caudate nucleus. Sham operation rats were injected with equal volume of saline. After the induction of ICH, the rats were randomly divided into four groups and administered with different dose of baicalin (0, 25, 50, or 100 mg/kg in saline) through peritoneal injection. The brain tissues around the hemorrhage areas were collected on days 1, 3, and 5 after treatment. Brain edema was analyzed by desiccation method; the metalloproteinase-9 (MMP-9) protein and mRNA expression were determined by western blotting and real time RT-PCR, respectively. Nuclear factor-κB (NF-κB) protein expression was analyzed by western blotting. IL-1β and IL-6 levels were determined by enzyme-linked immunosorbent assay. Blood-brain barrier permeability was determined by Evans blue leakage method. The results showed that baicalin reducedbrain edema following ICH in a dose-dependent manner, with concomitant inhibition of NF-κB activation and suppression of MMP-9 expression. In addition, baicalin also reduced IL-1β and IL-6 production, as well as blood-brain barrier permeability. The above results indicated that baicalin prevents against perihematomal edema development after intracerebral hemorrhage possibly through an anti-inflammatory mechanism.
Effect of baicalin on matrix metalloproteinase-9 expression and blood-brain barrier permeability following focal cerebral ischemia in rats.
Abstract
Focal cerebral ischemia results in an increased expression of matrix metalloproteinase-9 (MMP-9), which induces vasogenic brain edema via disrupting the blood-brain barrier (BBB) integrity. Recent studies from our laboratory showed that baicalin reduces ischemic brain damage by inhibiting inflammatory reaction and neuronal apoptosis in a rat model of focal cerebral ischemia. In the present study, we first explored the effect ofbaicalin on the neuronal damage, brain edema and BBB permeability, then further investigated its potential mechanisms. Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO). Baicalin was administrated by intraperitoneally injected twice at 2 and 12 h after the onset of MCAO. Neuronal damage, brain edema and BBB permeability were measured 24 h following MCAO. Expression of MMP-9 protein and mRNA were determined by western blot and RT-PCR, respectively. Expression of tight junction protein (TJP) occludin was detected by western blot. Neuronal damage, brain edema and BBB permeability were significantly reduced by baicalin administration following focal cerebral ischemia. Elevated expression of MMP-9 protein and mRNA were significantly down-regulated by baicalin administration. In addition, MCAO caused the decreased expression of occludin, which was significantly up-regulated by baicalin administration. Our study suggested that baicalin reduces MCAO-induced neuronal damage, brain edema and BBB permeability, which might be associated with the inhibition of MMP-9
http://www.ncbi.nlm....d brain barrier
Percutaneous absorption effects of Chinese herbal medicine
Yongzhan Bao1,2, Shaohua Zhang1,2 and Wanyu Shi1,2*
1College of Veterinary Medicine, Agricultural University of Hebei, Baoding 071001, China.
2
Institute of Traditional Chinese Veterinary Medicine, Agricultural University of Hebei, China.
Accepted 12 December, 2011
This study was carried out to evaluate the effects of Chinese herbal transdermal ointment on mastitis in
the dairy cow and to select the best efficient formula for treating the disorder. With chlorogenic acid as
a marker, using high performance liquid chromatography (HPLC), the contents of chlorogenic acid in
permeate liquid were determined. Different skin permeation enhancing effects of Chinese herbal
medicinal formulations and various herbal transdermal promoters were evaluated in the form of
ointment. The results indicated that ultrafined powder (UFP) of Chinese herbal medicine (CHM) directly
adding to medication and 4.5% borneol plus 4.5% Azone as skin permeation enhancers showed the
best skin-penetrating effect
Ordinarily, combination of two or more transdermal
promoters works synergistically in promoting drug
penetration through the skin with much better results than
one promotor alone. Thereby, combined use of
promoters will reduce the amount used of each promoter
with lower toxicity. Nitrogen ketones and borneol are the
common used penetration enhancers, and we have two
kinds of penetration enhancing effects of promotors
studied. From this experiment, we can see that borneol
and nitrogen mixed ketones showed the best penetration
or transdermal promoting effects, indicating that borneol
and Azone in the transdermal play a synergistic role in
helping the drug penetrate the skin. Borneol alone and
Azone alone, however, showed less transdermal effects.
The role of borneol was stronger than Azone, suggesting
a leading role of borneol and Azone as a supporting
partner. Complicated ingredients of Chinese herbal
compound, borneol partial fat-soluble and water-soluble
Azone, the two combined is conducive to the overall
absorption of active ingredients (Pan et al., 2006; Lin et
al., 2007).
https://drive.google...dit?usp=sharing
Borneol/Menthol used to increase flavonoid bioavailability
A borneol/menthol eutectic mixture has enhanced the brain transport of a drug when it was nasally coadministered with a polypeptide molecule (10). Daidzein (also called 4′,7-dihydroxylisoflavone) (Fig. 1), a water-insoluble isoflavone, is mainly present in leguminous plants, especially in soybeans, soy foods, and Pueraria lobata Ohwi (Leguminosae) (11,12). Daidzein can reduce breast cancer occurrence and also plays a key role in protecting against colon cancer (13). More recently, Wilcox and Blumenthal (14,15) have hypothesized that isoflavones may reduce the aggregation of platelets at the sites of arterial injury. These sites are associated with atherosclerotic development.
Compared with the daidzein suspension, the relative bioavailability of daidzein administered with borneol/menthol eutectic mixtures was 1.5-fold higher
http://www.ncbi.nlm....les/PMC3225554/
Ladies and gentlemen please stay tuned....
