# Use novel natural compound Sparstolonin B to treat bacterial sepsis

> **NIH NIH R41** · ACEPRE, LLC · 2021 · $300,000

## Abstract

Summary: According to the most recent CDC report, the incidence of sepsis in the United States is over 1.7
million each year, resulting in about 270,000 deaths and over $20 billion in healthcare costs. Sepsis results
from infection of any microorganisms with bacteria being the most common. Pathogen-associated molecular
patterns (PAMPs), such as lipopolysaccharides (LPS) activate innate immune cells, macrophages in particular,
as well as tissue resident cells such as vascular endothelial cells and cardiomyocytes through Toll-like
receptors (TLRs). The activated macrophages engulf and kill the microbes. On the one hand, this process may
reduce microbial load and limit the infection. On the other hand, these activated macrophages may elicit a
stronger than desirable inflammatory response by secreting excess amounts of cytokines and oxidative
molecules, acting on tissue resident cells and leading to tissue damage. Moreover, the damaged tissues
release endogenous damage-associated molecular patterns (DAMPs), which further escalate the inflammatory
cascade through binding to TLRs, particularly TLR2 and TLR4, on immune cells and tissue resident cells. This
vicious cycle rapidly leads to multi-organ injury, and eventually death. The quick evolution and the complexity
of the pathology of bacterial sepsis make it extremely difficult to treat. Current management still relies on
source control, antibiotics, and organ support. Although inflammation plays a key detrimental role in the
pathogenesis of septic shock, no anti-inflammatory approaches have been proved successful due to various
reasons. In the past 10 years, we and collaborators 1) isolated a new single compound from Chinese herbs,
determined its structure, and named it Sparstolonin B (SsnB); 2) characterized SsnB as a dual TLR2 and TLR4
antagonist; 3) discovered that SsnB antagonizes TLR2/4 by disrupting the interaction between TIRAP and
MyD88, a unique key event in TLR2/4 signaling; 4) demonstrated that SsnB effectively inhibits inflammatory
responses of multiple cell lines and primary cell types to both exogenous and endogenous TLR2/4 ligands; 5)
showed that SsnB inhibits the hypoxia-induced cardiomyocyte inflammatory response and apoptosis in cell
culture and in live heart slices; 6) reported that intraperitoneal administration of SsnB effectively reduced the
death of LPS endotoxemic mice; and 7) in most recent preliminary study demonstrated that SsnB prolonged
survival of male CD-1 mice using a cecal ligation and puncture (CLP) model. On the basis on these
achievements, we are in a unique position to develop SsnB as a novel therapy for bacterial sepsis. Toward this
goal, we propose in this STTR phase I project to establish the feasibility of clinical development. We propose
two specific aims: SA1. To establish the effectiveness of SsnB in various mouse strains using the CLP model
of bacterial sepsis; and SA2. To optimize the therapeutic regimen of SsnB to treat CLP-induced sepsis. We
believe thi...

## Key facts

- **NIH application ID:** 10152442
- **Project number:** 1R41AI157378-01
- **Recipient organization:** ACEPRE, LLC
- **Principal Investigator:** Hongkuan Fan
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2021-02-05 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152442

## Citation

> US National Institutes of Health, RePORTER application 10152442, Use novel natural compound Sparstolonin B to treat bacterial sepsis (1R41AI157378-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10152442. Licensed CC0.

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