# Clinical Pharmacology and Target Validation of BDPP for Stress-Related Disorders

> **NIH NIH U19** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $382,830

## Abstract

Project Summary/Abstract 
Stress is a leading risk factor for a multitude of the most prevalent mental health illnesses worldwide, including 
major depressive disorder (MDD). Current treatments fall short of what is required to meet the ever increasing 
disease burden and opportunity cost. In addition, current treatment paradigms fail to alleviate underlying 
pathophysiologies and a significant percentage of patients become refractory to treatment. The purpose of 
Research Project 2 is to investigate whether a well-characterized polyphenol enrich botanical supplement can 
provide an alternative approach to suppress the pathological effects of stress that increase an individual's 
susceptibility to developing certain psychiatric disorders. Emerging evidence has demonstrated that 
susceptibility to stress is a function of both central and peripheral immune activity. In particular, select 
inflammatory mediators, such as interleukin (IL)-6, have recently been recognized as key mechanistic 
contributory factors of stress-induced anxiety and depression. Supporting this principle are clinical 
observations that show that a subset of patients with treatment-resistant depression exhibit increased 
expression of IL-6 in the plasma. We show in a model system of stress-induced depression that specific 
bioavailable metabolites of our botanical supplement suppress stress-induced production of IL-6 from 
leukocytes and, further, provide resilience to stress-induced psychological impairment. Therefore, the first 
objective of Research Project 2 will be to thoroughly the pharmacokinetic and steady state properties of our 
botanical supplement to confirm that the bioactive compounds that were found to modulate IL-6 expression in 
rodents are also bioavailable and reach a bioactive concentration in humans. We will conduct a double blind, 
randomized, placebo-controlled (untreated control), dose ranging study in healthy volunteers using a low dose, 
intermediate dose, and high dose of BDPP, based upon our work with animals and from the scientific literature. 
Project 2 then investigate the association between metabolites of our botanical supplement and the expression 
of inflammatory cytokines in healthy subjects. Our proposed experiments will then characterize whether BDPP 
metabolites prevent upregulation of IL-6 in response to the Trier Social Stress Test: a well-validated model of 
psychological stress. Moreover, by integrating a multivariate adaptive regression splines (MARS) statistical 
method we can determine which metabolite, or combination of metabolites, may be responsible for 
suppressing IL-6 in a clinical setting in response to stress. Objectives from Research Project 2 will inform a 
future clinical trial by providing guidance on the optimal product dose, treatment timing, outcome markers of 
bioavailability; will verify metabolites that suppress IL-6 expression are present at bioactive concentrations in 
plasma, and establish whether anti-inflammat...

## Key facts

- **NIH application ID:** 10447074
- **Project number:** 5U19AT010835-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** James Warren Murrough
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,830
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447074

## Citation

> US National Institutes of Health, RePORTER application 10447074, Clinical Pharmacology and Target Validation of BDPP for Stress-Related Disorders (5U19AT010835-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10447074. Licensed CC0.

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