Phytotherapy and the Role of Bioactive Compounds in Modulating Mechanisms of Overweight and Obesity Comorbid with Depressive Symptoms-A Scoping Review of Mechanisms of Action

Molecules. 2025 Jun 30;30(13):2827. doi: 10.3390/molecules30132827.

Abstract

Obesity and depression frequently coexist, sharing overlapping molecular pathways such as inflammation, oxidative stress, gut microbiota dysbiosis, and neuroendocrine dysfunction. Recent research highlights the therapeutic potential of plant-derived bioactive compounds in targeting these shared mechanisms. This scoping review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included 261 peer-reviewed studies identified through PubMed, Scopus, and the Web of Science up to December 2024. Studies were screened based on predefined inclusion and exclusion criteria. This review synthesizes data from peer-reviewed studies, including both preclinical and clinical investigations, focusing on polyphenols, flavonoids, alkaloids, and other phytochemicals with anti-inflammatory, antioxidant, neuroprotective, and metabolic effects. Compounds such as quercetin, epigallocatechin gallate (EGCG), resveratrol, curcumin, anthocyanins, and luteolin demonstrate promise in modulating adenosine monophosphate-activated protein kinase (AMPK), brain-derived neurotrophic factor (BDNF), nuclear factor kappa B (NF-κB), and gut-brain axis pathways. Our scoping review, conducted in accordance with PRISMA guidelines, identifies promising combinations and mechanisms for integrative phytotherapy. These findings underscore the potential of botanical strategies in developing future interventions for metabolic and mood comorbidities.

Keywords: antioxidant mechanisms; bioactive compounds; depression; gut–brain axis; neuroinflammation; obesity; phytotherapy; polyphenols.

Publication types

  • Scoping Review

MeSH terms

  • Animals
  • Depression* / drug therapy
  • Depression* / metabolism
  • Gastrointestinal Microbiome / drug effects
  • Humans
  • Obesity* / complications
  • Obesity* / drug therapy
  • Obesity* / epidemiology
  • Obesity* / metabolism
  • Overweight* / drug therapy
  • Overweight* / metabolism
  • Phytochemicals* / pharmacology
  • Phytochemicals* / therapeutic use
  • Phytotherapy* / methods

Substances

  • Phytochemicals