Dehydroandrographolide inhibits mastitis by activating autophagy without affecting intestinal flora

Area of Science:

• Pharmacology and Immunology
• Microbiology
• Cell Biology

Background:

• Mastitis poses significant health risks to lactating women.
• Conventional treatments like antibiotics and anti-inflammatories can disrupt the gut microbiome.
• There is a need for treatments that alleviate mastitis while preserving flora balance.

Purpose of the Study:

• To investigate the anti-inflammatory and microbiome-balancing effects of dehydroandrographolide (Deh) for mastitis.
• To elucidate the molecular mechanism underlying Deh's anti-inflammatory action.

Main Methods:

• In vivo studies assessing mammary gland inflammation markers (MPO, IL6, IL-1β, TNF-α, COX2, iNOS) and pathological damage.
• 16S rRNA sequencing of fecal samples to analyze intestinal microflora composition.
• In vitro studies using EpH4-Ev cell lines to examine inflammatory marker expression and the role of AMPK signaling.
• Autophagy-related protein phosphorylation (AMPK, Beclin, ULK1) was assessed.

Main Results:

• Deh significantly reduced inflammatory markers and pathological damage in vivo.
• Deh did not alter the primary composition of the intestinal microflora.
• In vitro, Deh inhibited IL6, IL-1β, and TNF-α expression, an effect blocked by an AMPK inhibitor.
• Deh promoted autophagy by activating the AMPK/Beclin/ULK1 signaling pathway.

Conclusions:

• Dehydroandrographolide (Deh) exhibits potent anti-inflammatory effects relevant to mastitis treatment.
• Deh's anti-inflammatory mechanism involves activating the AMPK/Beclin/ULK1 pathway and promoting autophagy.
• Deh is a promising therapeutic agent for mastitis due to its efficacy and lack of adverse effects on intestinal flora.