<div>Background: Poekilocerus pictus (Fabricius 1771), a painted grasshopper, sequesters cardenolides from its food plant, the Apple of Sodom or Aak, Calotropis procera (Aiton) W.T. Aiton&nbsp; (Family-Asclepiadaceae). In our present investigation, we were able to isolate Pseudomonas aeruginosa KRK6 from the intestine of Poekilocerus pictus responsible for the biotransformation of cardenolides.&nbsp;</div>

<div>&nbsp;</div>

<div>Methods: Pseudomonas aeruginosa KRK6 was grown in methanolic extracts of Calotropis procera&nbsp; and the modified cardenolides were detected by Liquid Chromatography-Mass Spectrometry (LCMS) and also used to induce apoptosis in cancer cells (MCF-7 cells and T-47 D).&nbsp; 
 
Result: The modified cardenolides CPMEP6 was found to induce apoptosis in human breast adenocarcinoma cells (MCF cells-IC50 =6.31&plusmn;0.4 &micro;g/mL, T-47D cells-IC50 = 10.1&plusmn;1.02 &micro;g/mL). Phosphatidylserine exposure and DNA fragmentation suggested apoptosis in treated cancer cells. CPMEP6 induced apoptosis in cancer cells via the mitochondrial pathway by down-regulating BCL-2 protein expression and up-regulating BAX protein expression.</div>

Biotransformation of Cardenolides from Calotropis procera and Their Cytotoxic Potential against Human Mammary Gland Carcinoma Cells

The identification of&nbsp;acetovanillone (apocynin)&nbsp;in hydroethanolic extracts of&nbsp;Boophone disticha&nbsp;bulbs represents a notable advance in phytochemical profiling within South African Amaryllidaceae, a family traditionally recognized for its alkaloid diversity. This discovery is further expanded by evidence for acetovanillone in&nbsp;Crinum graminicola&nbsp;and&nbsp;C. buphanoides, alongside the exclusive detection of piceol in the latter, collectively extending the chemical landscape to aromatic, non-alkaloid phenolics. These compounds, characterized by mild vanilla-like aromas, highlight previously underappreciated facets of Amaryllidaceae&rsquo;s metabolic biodiversity. Importantly, acetovanillone&rsquo;s pronounced&nbsp;anti-inflammatory activity mediated via NADPH oxidase inhibition closely aligns with the documented ethno- pharmacological uses of these species for inflammatory conditions. Such phenolic antioxidants expand the pharmacognostic significance of Amaryllidaceae, supporting their therapeutic versatility beyond their alkaloidal content. Advancements in&nbsp;microbial biotransformation&nbsp;have shown Streptomyces tunisiensis can sustainably convert ferulic acid to acetovanillone, establishing new biosynthetic routes for industrial production and metabolic engineering targeting nutraceuticals and cosmeceuticals. Beyond plant systems, acetovanillone has shown robust&nbsp;neuroprotective potential, notably binding and inhibiting TDP-43, a protein linked to the pathogenesis of amyotrophic lateral sclerosis, with superior pharmacokinetic profile compared to clinically approved agents. In cardiovascular research, acetovanillone, alone and in combination with carvedilol, has demonstrated potent antioxidative and anti-inflammatory effects, modulating redox-sensitive signalling cascades and reducing myocardial injury. It suppresses NADPH oxidase expression and upregulates Nrf2, HO-1 and SIRT1, key protectors against oxidative cardiac damage, while attenuating inflammatory cytokines and necroptosis. Acetovanillone and its derivatives with antibacterial and antileishmanial activities have a wide range of applications like plant immunity, reproductive biology, hepatoprotection and chemoprevention, underscoring its utility as a chemotaxonomic marker and pharmacological lead for oxidative stress related disorders. Through extensive biochemical and molecular evidence, acetovanillone emerges as a multifaceted bioactive with promise for phytomedicine, drug development and quality control innovation in herbal formulations. 
&nbsp;

Biotransformation of Cardenolides from Calotropis procera and Their Cytotoxic Potential against Human Mammary Gland Carcinoma Cells

Acetovanillone (Apocynin): A Multifaceted Phenolic Compound with Therapeutic and Biotechnological Relevance