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Cited by 20Ovarian function and disordersReproductive Biology and FertilityNatural Antidiabetic Agents Studies

Targeting Polycystic Ovary Syndrome (PCOS) Pathophysiology with Flavonoids: From Adipokine–Cytokine Crosstalk to Insulin Resistance and Reproductive Dysfunctions

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Dutta, Sulagna, Sengupta, Pallav, Rao, Sowmya, Elgarawany, Ghada Elsayed, Samrot, Antony Vincent, Rosas, Israel Maldonado, Roychoudhury, Shubhadeep·2025·Pharmaceuticals
DOI 10.3390/ph18101575PMC PMC12567206
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Abstract

Polycystic ovary syndrome (PCOS) represents one of the most prevalent endocrine–metabolic disorder in women of reproductive age, which includes but not restricted to reproductive disruptions, insulin resistance (IR), hyperandrogenism, and chronic low-grade inflammation. Its heterogeneous pathophysiology arises from the interplay of metabolic, endocrine, and immune factors, including dysregulated adipokine secretion, cytokine-mediated inflammation, oxidative stress (OS), and mitochondrial dysfunction. Current pharmacological therapies, such as metformin, clomiphene, and oral contraceptives, often provide partial benefits and are limited by side effects, necessitating the exploration of safer, multi-target strategies. Flavonoids, a structurally diverse class of plant-derived polyphenols, have gained attention as promising therapeutic candidates in PCOS due to their antioxidant, anti-inflammatory, insulin-sensitizing, and hormone-modulating properties. Preclinical studies in rodent PCOS models consistently demonstrate improvements in insulin sensitivity, normalization of ovarian morphology, restoration of ovulation, and reduction in hyperandrogenism. Human clinical studies, though limited in scale and heterogeneity, report favorable effects of flavonoids such as quercetin, isoflavones, and catechins on glucose metabolism, adipokine balance, inflammatory markers, and reproductive functions. This evidence-based study critically synthesizes mechanistic insights into how flavonoids modulate insulin signaling, adipokine–cytokine crosstalk, OS, and androgen excess, while highlighting translational evidence and emerging delivery systems aimed at overcoming bioavailability barriers. Collectively, flavonoids represent a promising class of nutraceuticals and adjuncts to conventional therapies, offering an integrative strategy for the management of PCOS.

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  • The extent of the effect of ecdysteroids on plasma testosterone levels depends on dose, bioavailability, individual microbiome composition and genetic factors, making it difficult to draw uniform conclusions about the overall effect on plasma testosterone levels.

    “It is known from the literature data that the extent of the effect of ecdysteroids on plasma testosterone levels depends on dose, bioavailability, individual microbiome composition and genetic factors, making it difficult to draw uniform conclusions about the overall effect on plasma testosterone levels [49,50].”

    From Prevention of Diet-Induced Obesity by Phytoecdysteroids 20-Hydroxyecdysone and Calonysterone—Unexpected Modulation of Androgen Balance in Normal and Obese Rats (2026) · cites this paper as [50]

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Authors
Dutta, S., Sengupta, P., Rao, S., Elgarawany, G. E., Samrot, A. V., Rosas, I. M., & Roychoudhury, S.
Affiliations
  • Ajman University (AE)
  • Gulf Medical University (AE)
  • Manipal Academy of Higher Education, Dubai (AE)
  • Manipal University College Malaysia (MY)
  • Citmer Reproductive Medicine, Mexico City 11520, Mexico
  • Assam University (IN)
Corresponding author
  • Sengupta, Pallav
  • Roychoudhury, Shubhadeep
ORCID
Venue
Pharmaceuticals
Publisher
MDPI AG
Published
2025-10-18
Volume
18
Issue
10
Pages
1575
ISSN
1424-8247 (ISSN-L)
DOI
10.3390/ph18101575
PMC
PMC12567206
OpenAlex
W4415362164
Cited by
20
References
137
Citations by year
2026: 20
FWCI
2.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmaceuticals (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
Keywords
polycystic ovary syndrome, flavonoids, insulin resistance, oxidative stress, mitochondrial dysfunction, hyperandrogenism, reproductive disorders, quercetin, isoflavones, catechins, insulin signaling, nutraceuticals, bioavailability, inflammation

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