Salvianolic Acid E Senolysis for Chemotherapy-Induced SASP

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Solution Overview

Problem

Existing senolytic drugs are limited in their ability to effectively target and eliminate multiple types of senescent cells, leading to varying efficacy across different cell types and often failing to address the senescence-associated secretory phenotype (SASP) induced by chemotherapeutic drugs, which can promote tumor growth and resistance.

Innovation Solution

The use of salvianolic acid E in combination with chemotherapeutic drugs, such as mitoxantrone, doxorubicin, and bleomycin, to induce a senescence-associated secretory phenotype in the tumor microenvironment, specifically targeting and eliminating senescent cells while inhibiting tumor growth.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing senolytic drugs are used to target and eliminate senescent cells, then the survival rate of senescent cells is reduced, but the efficacy varies across different cell types and the senescence-associated secretory phenotype (SASP) induced by chemotherapeutic drugs is not effectively addressed

Engineering Contradiction:

Improveefficacy of senolytic drugsVSAvoidability to target multiple types of senescent cells

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines salvianolic acid E with chemotherapeutic drugs to create a synergistic treatment approach. This combination merges the senolytic activity of salvianolic acid E with the tumor-killing capabilities of chemotherapeutic agents, thereby effectively targeting multiple types of senescent cells while addressing the SASP induced by chemotherapy. The combined formulation resolves the limitation of single-agent senolytic drugs that fail to address chemotherapy-induced senescence.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

Salvianolic acid E exhibits multi-functional activity: it acts as a senolytic agent to eliminate senescent cells, an anti-SASP agent to suppress the secretory phenotype, and a chemosensitizing agent to enhance chemotherapeutic efficacy. This multi-functionality enables a single compound to address multiple aspects of senescence and tumor progression, improving both reliability and adaptability across different cell types and disease stages.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If chemotherapeutic drugs are used to treat tumors, then tumor growth is inhibited, but the senescence-associated secretory phenotype is induced which can promote tumor growth and resistance

Engineering Contradiction:

Improvetumor inhibition efficacyVSAvoidsenescence-associated secretory phenotype

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful SASP induced by chemotherapeutic drugs into a beneficial target. By using salvianolic acid E to specifically inhibit SASP factors (such as IL-6, IL-8, TNF-α) while maintaining the tumor-killing effects of chemotherapy, the approach transforms the harmful senescence response into a controlled process that reduces tumor growth and resistance without compromising the therapeutic benefits of chemotherapy.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Quantity of substance

If senolytic drugs are used to eliminate senescent cells, then the burden of senescent cells is reduced, but the drugs are limited in their ability to effectively target and eliminate multiple types of senescent cells

Engineering Contradiction:

Improvenumber of senescent cells eliminatedVSAvoidtargeting capability across different cell types

Core Design Contradiction:

Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The patent utilizes parameter changes in the chemical structure and pharmacological properties of salvianolic acid E to achieve broad-spectrum senolytic activity. By optimizing the compound's molecular characteristics and dosing parameters, the formulation achieves effective targeting across multiple senescent cell types (e.g., fibroblasts, endothelial cells, adipocytes) while maintaining selectivity and reducing off-target effects.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20250295619A1Use of Salvianolic Acid E in the Preparation of Drugs Targeting Senescent Cells, Inhibiting Tumors or Extending Lifespan

Publication Date: 2025.09.25 SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI

AI summary

The present disclosure provides a use of salvianolic acid E (SAE) in the preparation of drugs targeting senescent cells, inhibiting tumors or prolonging lifespan. The inventors are committed to research in screening drugs targeting tumor microenvironment, enhancing the anti-tumor effect of chemotherapeutic drugs, eliminating senescent cells or restraining cellular senescence. Here, it is revealed that salvianolic acid E exerts its effects by targeting tumor microenvironment and eliminating senescent cells. When combined with chemotherapeutic drugs, it shows extremely significant effects in promoting tumor suppression by removing senescent stromal cells. For a senescence-associated secretory phenotype (SASP), the SAE can also effectively target senescent cells so as to inhibit the SASP. Besides, the SAE can also significantly prolong the life of animals, significantly extend the survival period of the old and improve the life quality of animals.