Optimization of ex vivo permeability characteristics of berberine in presence of quercetin using 32 full factorial design

The aim of the present work was to investigate permeability characteristics of an anticancer berberine chloride, inpresence and absence of bioenhancer quercetin on goat intestine using Franz diffusion cell. A 32 full factorial designapproach was employed to investigate the effect of independent variables such as the concentration of bioenhancer(X1) and pretreatment time (X2) on dependent variable % cumulative drug release (% CDR) (Y) using design expertsoftware. The effect of quercetin was examined at three different levels of pretreatment time (30, 45, and 60 minutes)and at three different concentrations (2, 6, and 10 mg) on goat intestine. The apparent permeability (Papp), flux (J), andenhancement ratio (ER) were determined. Further, in vitro anticancer activity of optimized batch was performed onvarious cancer cell lines K562, A459, and Hela. During pretreatment studies, it was observed that an increase in theconcentration of quercetin yielded a positive effect on % CDR while the increase in pretreatment time by quercetinhad a detrimental effect on % CDR. When goat intestine was pre-treated for 30 minutes with 10 mg of quercetin,90.91% ± 1.66% CDR was obtained while the minimum value of 17.45% ± 2.12% CDR was observed at 2 mgquercetin pre-treated for 60 minutes. In vitro anticancer activity of optimized batch demonstrated non-significanteffect as compared with parent drug. In conclusion, quercetin could be successfully utilized as bioenhancer to improveex vivo permeability of berberine chloride, which would be expected to improve its bioavailability and reduce the doseresulting in improved patient compliance.

Evaluation of the effect of piperine per se and its interaction with ondansetron on haloperidol induced catalepsy in Albino mice

Background: This study aims to evaluate the per se effect of piperine and its interaction with ondansetron on haloperidol induced catalepsy in swiss albino mice.Methods: The piperine crystals were separated from crude extract of Piper nigrum. Catalepsy was induced by haloperidol (1mg/kg, i.p.). Control group received 2% gum acacia (10ml/kg), standard group ondansetron (0.5mg/kg), test group piperine (10mg/kg) and combination group ondansetron plus piperine (0.5mg/kg + 10mg/kg), per oral, respectively. In acute study, drugs were administered only once, one hour prior to the haloperidol administration. Whereas in chronic study, catalepsy was determined on the seventh day of treatment.Results: In acute study, from 60 min onwards after haloperidol administration, ondansetron and ondansetron plus piperine group resulted in significantly lower cataleptic scores than the control treated group. On the other hand, 120 min onwards ondansetron group showed significantly lower cataleptic scores (24.62) as compared to the ondansetron plus piperine group (31.50). In the chronic study, from 60 min onwards, ondansetron and the ondansetron plus piperine resulted in significantly lower cataleptic scores than the control treated group. Also the combination of ondansetron plus piperine was more significantly protective compared to ondansetron alone (P <0.05).Conclusions: Piperine has the potential to be used as a bioenhancer when combined with other drugs which would reduce the dose of drugs and thereby adverse effects. It may act probably by enhancing the bioavailability as well as by inhibiting the metabolic pathways of other drugs.

Enhancement of oral bioavailability and immune response of Ginsenoside Rh2 by co-administration with piperine / 中国天然药物

Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides in Panax ginseng. However, the oral bioavailability of Rh2 is low, with P-glycoprotein (P-gp) and CYP3A4 being reported to be the main factors. The purpose of the present study was to determine the enhancing effect of piperine on the oral bioavailability as well as bioactivity of Rh2. The inhibitory effect of piperine on P-gp and CYP3A4 was determined using a Caco-2 monolayer model and a recombinant CYP3A4 metabolic system, respectively. The pharmacokinetics of oral Rh2 (10 mg·kg) administered alone or in combination with piperine (10 and 20 mg·kg) was performed in rats. The immune boosting effect of Rh2 was assessed in rats by measuring IL-12 level after treated by Rh2 alone or co-administered with piperine. The results indicated that piperine significantly increased the permeability of Rh2 and inhibited the metabolism of Rh2. The pharmacokinetic study results showed that the AUC of Rh2 was significantly increased in combination with piperine at high dose (20 mg·kg) when compared to the control group, with relative bioavailability of 196.8%. The increase of Rh2 exposure led to increased serum levels of IL-12. In conclusion, piperine may be used as a bioenhancer to improve pharmacological effect of Rh2 when given orally.

Enhancement of oral bioavailability and immune response of Ginsenoside Rh2 by co-administration with piperine / 中国天然药物

Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides in Panax ginseng. However, the oral bioavailability of Rh2 is low, with P-glycoprotein (P-gp) and CYP3A4 being reported to be the main factors. The purpose of the present study was to determine the enhancing effect of piperine on the oral bioavailability as well as bioactivity of Rh2. The inhibitory effect of piperine on P-gp and CYP3A4 was determined using a Caco-2 monolayer model and a recombinant CYP3A4 metabolic system, respectively. The pharmacokinetics of oral Rh2 (10 mg·kg) administered alone or in combination with piperine (10 and 20 mg·kg) was performed in rats. The immune boosting effect of Rh2 was assessed in rats by measuring IL-12 level after treated by Rh2 alone or co-administered with piperine. The results indicated that piperine significantly increased the permeability of Rh2 and inhibited the metabolism of Rh2. The pharmacokinetic study results showed that the AUC of Rh2 was significantly increased in combination with piperine at high dose (20 mg·kg) when compared to the control group, with relative bioavailability of 196.8%. The increase of Rh2 exposure led to increased serum levels of IL-12. In conclusion, piperine may be used as a bioenhancer to improve pharmacological effect of Rh2 when given orally.

Bioavailability enhancers of herbal origin：An overview

Recently, the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines. However, many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size, resulting in poor absorption and hence poor bioavailability. Nowadays with the advancement in the technology, novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems. For last one decade many novel carriers such as liposomes, microspheres, nanoparticles, transferosomes, ethosomes, lipid based systems etc. have been reported for successful modified delivery of various herbal drugs. Many herbal compounds including quercetin, genistein, naringin, sinomenine, piperine, glycyrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability. The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs (herbal), and to achieve better therapeutic response. An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action (wherever reported) and studies on improvement in drug bioavailability, exhibited particularly by natural compounds.

Bioavailability enhancers of herbal origin: an overview

Recently, the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines. However, many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size, resulting in poor absorption and hence poor bioavailability. Nowadays with the advancement in the technology, novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems. For last one decade many novel carriers such as liposomes, microspheres, nanoparticles, transferosomes, ethosomes, lipid based systems etc. have been reported for successful modified delivery of various herbal drugs. Many herbal compounds including quercetin, genistein, naringin, sinomenine, piperine, glycyrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability. The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs (herbal), and to achieve better therapeutic response. An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action (wherever reported) and studies on improvement in drug bioavailability, exhibited particularly by natural compounds.

Bioenhancers: Revolutionary concept to market.

Treatment cost is a major concern for modern medicine in developing countries like India and systematic innovative means to reduce these costs are needed. This article reviews the concept of bioenhancers to reduce treatment costs by increasing drug bioavailability. This concept, based on the Ayurvedic system of medicine, works for a wide range of ingested substances, and has been applied to modern drugs, particularly single chemicals. It offers a fine example of the benefit of integrating an ancient system with modern medicine in both theory and practice.