# In vitro cobalt stress alters Adhatoda vasica anatomy, antioxidant defense, and metabolite profiles with docking insights

## TL;DR

This study shows how cobalt stress affects the growth, structure, and chemical makeup of the medicinal plant Adhatoda vasica, with implications for its use in herbal medicine and cancer treatment.

## Contribution

The study reveals how cobalt stress alters plant anatomy, antioxidant defenses, and metabolite profiles, with new insights into naringin’s potential for skin cancer treatment.

## Key findings

- Low cobalt concentrations increased shoot dry weight, while higher concentrations reduced it significantly.
- Cobalt exposure altered antioxidant enzyme activity and secondary metabolite profiles in a dose-dependent manner.
- Naringin showed higher binding affinity to a skin cancer-related protein compared to other metabolites.

## Abstract

The growing demand for medicinal plants in herbal medicine highlights their therapeutic value, yet heavy metal contamination, such as cobalt (Co), poses potential health risks. Cobalt’s dual role as an essential micronutrient and a toxic pollutant necessitates a more profound understanding of its impact on medicinal plants like Adhatoda vasica. We investigated how varying Co concentrations affect A. vasica shoot growth, leaf anatomy, antioxidant enzyme activity, and secondary metabolite profiles. Additionally, molecular docking was performed to assess the interaction of the metabolites with the skin cancer-related protein anti-ssDNA antigen-binding fragment (PDB code: 1P7K). Low Co concentrations (50 µM) enhanced shoot dry weight by 41.45%, while higher levels (100–1000 µM) reduced it by up to 66.86%. Cobalt exposure increased hydrogen peroxide (H2O2) and lipoxygenase (LOX) activity, indicating reactive oxygen species (ROS)-induced oxidative stress. Higher Co levels increased superoxide dismutase (SOD), catalase (CAT), phenylalanine ammonia-lyase (PAL), and polyphenol oxidase (PPO) but decreased peroxidase (POD) and ascorbate peroxidase (APX) activity. HPLC-UV and GC-MS data showed that Co altered the secondary metabolites of A. vasica, including phenolics, flavonoids, alkaloids, and terpenoids, in both qualitative and quantitative ways. Molecular docking shows that naringin has a higher binding affinity (-9.2 kcal/mol) to PDB: 1P7K than phenolics (-4.8 to -6.4 kcal/mol). Cobalt stress significantly impacts A. vasica, altering its leaf structure, growth, and antioxidant defenses. These effects extend to secondary metabolites in a dose-dependent manner. These findings highlight the plant’s potential for Co tolerance and its metabolites’ therapeutic promise, particularly naringin, for skin cancer applications.

The online version contains supplementary material available at 10.1186/s12896-025-01088-9.