Curcumin as Therapeutic Modulator of Impaired Antioxidant Defense System: Implications for Oxidative Stress-Associated Reproductive Dysfunction

Abstract

One of the critical challenges in assisted reproductive technology (ART) is the inadequacy of effective regulation of reactive oxygen species. Simultaneously, the endogenous antioxidant defense system plays a significant role in combating oxidative stress across various physiological stages of embryonic development. However, these intrinsic defense systems alone are insufficient as they rely on exogenous antioxidants that interact synergistically to enhance and sustain antioxidant capacity. Considering the principal role of antioxidants in mitigating oxidative stress in oocyte growth, identifying reliable and non-toxic antioxidants is an essential prerequisite for effective therapeutic applications. Thus, owing to the need to explore exogenous antioxidants, we attempted to summarize and analyze the literature data defining the potential use of curcumin in mitigating oxidative stress to promote oocyte maturation through in vivo and in vitro model studies. Recent studies demonstrated the protective role of curcumin against oxidative stress and the inflammatory response, primarily through the upregulation of key antioxidant enzymes (including SOD, CAT and GPx), a reduction in oxidative stress markers (e.g., ROS, MDA) and by suppressing the pro-inflammatory signaling pathways (such as NF-kB, JAK/STAT) while activating the NRF2/HO-1 pathway to further enhance the cellular antioxidant defense. Advancing curcumin as a therapeutic agent necessitates a thorough understanding of curcumin's molecular mechanisms and targeted pharmacological effectiveness to treat female infertility, and despite the progress in enhancing curcumin's bioavailability, the optimal dosing strategies still need to be defined. Future studies are required to develop strategies to augment antioxidant defense mechanisms (modeling in vivo and in vitro studies) using curcumin with a specific emphasis on curcumin's role in improving mitochondrial activity. This approach is expected to represent a significant advancement in the field of medicine, offering novel therapeutic possibilities.

Keywords: antioxidants; curcumin; female infertility; follicle growth; oxidative stress.

Figure 1

Overview of bioactivities of antioxidants and the associated health benefits of curcumin.

Figure 2

Classification of antioxidants based on their origin and mode of action, demonstrating curcumin as naturally occurring non-enzymatic exogenous antioxidant.

Figure 3

Schematic representation of two contrasting cycles: the impaired antioxidant defense mechanism leading to cellular damage and infertility and the effects of curcumin in attenuating ROS levels through multiple signaling pathways (↑ represents an increase; ↓ represents a decrease).

Figure 4

Inclusive profile of Curcuma longa, illustrating curcumin and the other two curcuminoids (DMC and BDMC) along with their distinguishing characteristics [87,88,89].

Figure 5

(a) Effects of different curcumin concentrations on ovarian follicle development under oxidative stress conditions [105,106,107]. (b) Curcumin-mediated enhancement of endogenous antioxidant enzyme activity under oxidative stress conditions [105,107,111]. (c) Curcumin-mediated cellular oxidative balance under oxidative stress conditions [107,111].

Figure 5

(a) Effects of different curcumin concentrations on ovarian follicle development under oxidative stress conditions [105,106,107]. (b) Curcumin-mediated enhancement of endogenous antioxidant enzyme activity under oxidative stress conditions [105,107,111]. (c) Curcumin-mediated cellular oxidative balance under oxidative stress conditions [107,111].