INTRODUCTION:

There are number of drugs available which has very profound pharmacological activity but they are unable to give good results because they have difficulties in their physical and chemical properties like solubility, ph, absorption, bioavilability as well as chemical configuration here curcumin is an example of this category curcumin has ability to treat many pathological conditions the main effective property is anti oxidative property because the root cause of many diseases is oxidative stress (Soheil Z M,et al,2014). It also enhance the activity of biological antioxidants and neutralize the lipid peroxidation,

its enol form is more stable and protect bio-membrane by ROS scavenging Kishu Tripathi et al but because of its poor bioavilability (Suman Saha et al) it has to be prescribed in higher dose (Mohammad H F et al,2018).Curcumin is phytoconstituent of Turmeric which is famous as Indian spice(Sweetha G et al) and principle ingredient of curry powders the botanical source of turmeric is roots of Curcuma longa from Zingiberaceae family Krishna Veni Nagappan, fresh turmeric root is used in daily life across the South east Asia not only as spice for medical conditions also, and turmeric is a common drug for numerous diseases in Indian Ayurvedic medicine from thousands of years this is also use as flavor and to give color to food (Sourav B,at el,2018). In 1815 curcumin was isolated and in 1870 it formulated in to crystalline form(Matthew C F et al, 2017) but because of low aqueous solubility (P. Venugopalan), high intestinal as well as hepatic metabolism and high renal clearance which limits the therapeutic use of Curcumin(C. Moorthi et al,2013).

In research there is evidence that high-dose of curcumin for long time will initiate cancer in rodents and its antioxidant property turns into pro-oxidant when concentration is high. This inverse effect of curcumin give explanation to quasi opposite effects on biological systems. To avoid this problem bioenhancers can be used with Curcumin such as Quercetin(Jenny E et al,2010).Quercetin is a Flavonol type of flavonoid Ashok Kumar BS et al and this molecule is abundantly present in plants, in that especially in citrus fruits and onions and its small amount is also present in apples, berries, Brassica vegetables, grapes, capers, tomatoes, shallot, and tea (A. Thennarasu et al). Most of the Quercetin flavonols are glycosides which separated according to its sugar linkage for example quercetin glucoside and quercetin rutinoside(Gregory S. K,2011).

It is stated that quercetin has ability to enhance bioavilability of most of the drugs it enhance the bioavilability by enhancing the drug concentration in blood through inhibition of drug metabolism and its systemic clearance the plasma concentration time curve and peak concentration of many drugs is higher when those drugs given in combination with quercetin because Quercetin extent the bioavilability of drug by inhibition of P-glycoprotein and metabolic enzymes like CYP3A4 enzyme(Kritika K et al, 2013).There is chances that it will also enhance the bioavilability of curcumin because curcumin has poor solubility and because of that its absorption is also very less, when it absorb into the cell it will metabolize or efflux out from the cell², quercetin is a bioenhancer and it has ability to enhance the absorption of some natural drugs like epigallocatechin gallate (Anup K et al, 2010, Vaishnavi C K, 2017) so it can also enhance the absorption of curcumin into the intestinal lumen by opening tight junction between cells of cell wall of intestine as well as it can block the efflux pump which is present on the surface of cell membrane and also inhibit metabolic enzymes (Ghanshyam B. D et al, 2017) which are responsible for curcumin metabolism. So here we conclude that quercetin may enhance the absorption of curcumin into the intestine by minute modification of cell membrane and increase its bioavilability.

MATERIAL AND METHOD:

Material:

Curcumin was purchased from Natural Herbals and Healthcare Gandhidham Kutch Gujarat India. Quercetin was purchased from Yuka Herbals Vododara India, for experimental procedures distilled water was used and chemical with analytical reagent grade. Chicken intestine was arranged from local chicken shop within one hour after killing of chicken.

Preparation of Physiological Salt Solution:

Tyroid salt solution was used to maintain physiological condition prepared by as per previous research articles and experimental book of pharmacology by Kulkarni (V.R.Undale,et,al,2012).

Preparation of standard and test sample:

200 mg curcumin was used as standard and 100mg curcumin with 50mg quercetin as test and other dilutions of curcumin and quercetin were prepared (2µg, 3µg, 4µg, 6µg ,8µg, 10µg)for calibration curve and calculation of q equation (AS Langdeet et al) to obtain calculated data by UV spectroscopy(Gitu Pandey,et al,2013) Paras Viraniet al.

Preparation of chicken Intestine:

In-vitro permeability study of curcumin was studied by taking a fresh section of chicken intestine in Tyroid salt solution to maintain physiological conditions the jejunum and ileum was taken because in humans this area is responsible for high absorption. Tow Fresh section of chicken small intestine was taken and cleaned with tyroid salt solution the size of the tissue was 6 cm in length, by continues oxygen supply with aerator tissue was kept alive for 4 hour in physiological salt solution and both end of tissue was tied with thread and installed with drug solution one section was installed with 200mg curcumin and another one was installed with 100mg curcumin in combination with 50mg quercetin minimum 2 ml of drug solution was installed and both the tissues were tied vertically in 1000 ml of tyroid solution with continuous stirring at 20rpm at 37ºC±1 temperature with continuous oxygen supply with aerator as in figure no.1, at 1hour interval 2ml of sample was taken from assembly and same amount of tyroid solution was add, this continued for three hours then sample was analyzed in UV spectroscopy(Remeth Dias et,al,2010).

Figure;1 Assembly of In-vitro study

Statistical Analysis:

Here we were used q-equation for statistical analysis because there are two different drugs curcumin and quercetin and they analyzed in UV Spectroscopy, and for computer analysis pro0.5 software was used, so for q-equation two different wavelengths were needed one represent the λmax of one of the two component and other represent the isoabsorptive point of both the drugs, for experimental part we used 200 and 100mg of curcumin and 50 mg of quercetin and for analysis part we took 0.6µg of curcumin and 0.3µg of quercetin these concentrations were obtained from the calibration curve of both the drugs in figure no.2 (Gurmeet S et,al,2012).The absorption spectrum of curcumin and quercetin as mentioned in figure 3 and figure 4, both the spectrum overlapped on each other at 255 nm which is isoabsorptive point.

Figure: 2 Standard absorbance curve of curcumin

Regression value= 0.98 and a linear curve was obtained.

Figure: 3 Absorbance graph of 6 µg curcumin at 285nm

UV range200-400nm

Figure;4 Absorbance graph of 3 µg quercetin at 285nm

UV range200-400nm

After experiment the slope and regression values for both the drug at both wavelength was different as in the table number 1, and we can see the difference between the concentration of curcumin in assembly1 with200mg curcumin alone and assembly with 100mg curcumin and 50mg quercetin from the table2 and table3.

Table: 1 intercept and regression value of curcumin and quercetin at different ƛ max

Drug

Y intercept R²andregression at 285nm

Y intercept and R²regression at 255nm

Curcumin

0.033x – 0.015

R² = 0.984

0.046x + 0.013

R² = 0.871

Quercetin

0.055x + 0.004

R² = 0.974

0.046x + 0.240

R² = 0.910

Y=mx+b (m=slope, b= Intercept),(R²= correlation coefficient, Y=regression equation

Table 2 Concentration and absorbance of 200mg curcumin at different time interval from the chicken intestine

Sr. no.	Absorbance at different time interval (hour)	Concentration (mg/ml)
1	1 hour	1.093
2	2hour	1.294
3	3hour	2.479
4	4hour	4.515

Tabel: 3 By using Q equation the concentration of both the drugs in assembly 2 in different time interval

Sr. no.	Time (in hours)	Curcumin concentration(mg)	Quercetin concentration (mg)
1	1	7.95	2.86
2	2	8.79	3.15
3	3	10.17	3.65
4	4	12.51	4.49

RESULT:

Two different assemblies were used for the experiment one with 200mg curcumin and another with 100mg curcumin and 50mg quercetin and chicken ileum were used as biological barrier, experiment was continued for 4 hours and 2ml sample analyzed. After UV analysis the concentration of curcumin is increased in different time interval (7.95mg, 8.79mg, 10.17mg, 12.51mg) in the presence of quercetin by this we can estimate that the absorption of curcumin is increased. In absences of quercetin the concentration was 1.093 in 1 hour and in presence of quercetin concentration was 7.95 in 1 hour this difference gives the evidence about increased absorption rate of curcumin. Increased absorption will leads to increased bioavilability.

DISCUSSION:

Curcumin is a spice which has so many therapeutic values like anti inflammatory, anti microbial, anti mutagenic, and helpful in cancer treatment because of its antioxidant property (Hwa-Young Lee et,al,2016). It has many beneficial properties but its bioavailability is very poor due to number of reasons those are poor solubility, low absorption rate, metabolic elimination from body(Susan J. Hewlings, 2017, Michele Dei Cas et al,2019, Arnab Samanta et al), nowadays curcumin dose is very high 8000mg to 12000mg due to its poor bioavailability which is unpleasant to patient because of bulky volume(Christopher D Lao et al,2006)which can be reduced by enhancing the bioavilability as already stated that absorption of drug is directly proportional to its bioavilability means if absorption of drug enhanced than bioavilability will also increase(Kd Tripathi,2013).quercetin is a potential bioenhancer which enhance the bioavilability of drugs by inhibition of metabolic enzymes and P-glycoprotein efflux pump inhibition (Rachana Bhimanwar et al, 2020), concentration of berberine was enhanced by (Sarika Narade et.al, 2019) and some other researcher also approved the bioenhancing property of quercetin²¹; it is effective on the bioavailability of many drugs like pioglitazone, diltiazem, paclitaxel, tamoxifen, digoxin, verapamil, etoposide etc(Chander PalSVet al,2019). Here we can see the difference in the concentration of curcumin in the biological fluid when it is alone its concentration is very low and with quercetin its concentration is high which indicates the curcumin absorbance through intestine is increased in the presence of quercetin.

AUTHORS CONTRIBUTION:

Dr. Jagdish Kakadiya gathered the information and Aditi patel helped in the analysis part of the research work and all the authors discussed the all data related to methodology and result and contributed to final manuscript. The authors declare that they have no conflict of interest.

CONCLUSION:

Curcumin is insoluble in water and soluble in organic solvent and it has good therapeutic value but because of poor solubility in water its absorption is also poor which leads to low bioavilability. This experiment states the quercetin can enhance the absorption of curcumin through the intestine. Bioavilability of drugs is related to absorption of drug if a drug has good absorption then its bioavilability is also good. At the dose of 50 mg quercetin enhance the absorption of curcumin from the intestine. By this experiment curcumin absorption was increased in to the intestine by quercetin it can also increase bioavilability of curcumin to confirm that further study is necessary.

FUNDING SUPPORT:

The authors declare that they have no funding support for this study.

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Received on 25.01.2021 Modified on 13.11.2021

Research J. Pharm. and Tech 2022; 15(11):4867-4870.

DOI: 10.52711/0974-360X.2022.00817