[25] The gonadotropin releasing hormone conjugate has a deleterio

[25] The gonadotropin releasing hormone conjugate has a deleterious selleck chem effect on the reproductive hormones and estrous cycle of female mice; and cow urine distillate acts as a bioenhancer in immunization efficacy to modulate these effects.[49] Cow urine has antitoxic activity against the cadmium chloride toxicity and it can be used as a bioenhancer of zinc. Mature male mice, Mus musculus, exposed to cadmium chloride only, showed 0% fertility rate. Fertility index increased to 88% in the group treated with cow urine along with cadmium chloride. However, the animals exposed to cadmium chloride + cow urine + zinc sulfate showed 90% fertility rate with 100% viability and lactation indices.

[50] MECHANISM OF ACTION OF BIOENHANCERS Bioavailability-enhancing activity of natural compounds from the medicinal plants may be attributed to various mechanisms, such as P-gp inhibition activity by flavone, quercetin, and genistein;[51] inhibition of efflux transporters, such as P-gp and breast cancer resistance protein (BCRP),[52,53] by naringin and sinomenine thus preventing drug resistance; DNA receptor binding, modulation of cell signaling transduction, and inhibition of drug efflux pumps[54�C56]; by stimulating leucine amino peptidase and glycyl-glycine dipeptidase activity, thus modulating the cell membrane dynamics related to passive transport mechanism as seen with piperine[57]; nonspecific mechanisms, such as increased blood supply to the gastrointestinal tract, decreased hydrochloric acid secretion, preventing breakdown of some drugs[6]; and inhibition of metabolic enzymes participating in the biotransformation of drugs, thus preventing inactivation and elimination of drugs and thereby, increasing their bioavailability.

[57�C59] FUTURE PERSPECTIVES Taking leads from ayurveda and other traditional ways of medicine is nothing new for a modern researcher. Origin of about 75% of antimicrobial and 60% of anticancer drugs approved for clinical use from 1981 to 2002 could be traced back to nature.[60] It has taken lead from the use of ��trikatu�� as a bioenhancer from ayurveda and successfully applied it to various modern medicines to enhance their bioavailability. The ayurvedic concept of anupaan and sehpaan ought to be incorporated into the modern medicine also. Modern medicine can take the cue from the ayurvedic leads to develop more efficacious and safe medicines with safer routes of drug administration in future also.

The underlying mechanisms with their clinical outcomes can also be researched and validated further as per the latest research methodologies. Footnotes Source of Support: Nil. Conflict of Interest: None declared.
Estrogen receptor (ER) is the GSK-3 most important prognostic and predictive marker for breast cancer.[1] Presence of both ER and progesterone receptor (PgR) is related to better prognosis and responsiveness to hormonal therapy.

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