Abstract
Polyphenols are widely known for their antioxidant activity, i.e., they have the ability to suppress oxidative stress, and this behavior is mediated by the autoxidation of their phenolic hydroxyl groups. Postmenopausal osteoporosis is a common health problem that is associated with estrogen deficiency. Since oxidative stress is thought to play a key role in the onset and progression of osteoporosis, it is expected that polyphenols can serve as a safe and suitable treatment in this regard. Therefore, in this review, we aimed to elucidate the anti-osteoporotic mechanisms of polyphenols reported by in vivo studies involving the use of ovariectomized animals. We categorized the polyphenols as resveratrol, purified polyphenols other than resveratrol, or polyphenol-rich substances or extracts. Literature data indicated that resveratrol activates sirtuin 1, and thereafter, suppresses osteoclastogenic pathways, such as the receptor activator of the nuclear factor kappa B (RANK) ligand (RANKL) pathway, and promotes osteoblastogenic pathways, such as the wingless-related MMTV integration site pathway. Further, we noted that purified polyphenols and polyphenol-rich substances or extracts exert anti-inflammatory and/or antioxidative effects, which inhibit RANKL/RANK binding via the NF-κB pathway, resulting in the suppression of osteoclastogenesis. In conclusion, antioxidative and anti-inflammatory polyphenols, including resveratrol, can be safe and effective for the treatment of postmenopausal osteoporosis based on their ability to regulate the imbalance between bone formation and resorption.
Highlights
The World Health Organization (WHO) has defined osteoporosis as a disease characterized by low bone mass and bone tissue microarchitectural deterioration that leads to enhanced bone fragility and a consequent increase in fracture risk [1]
Recent studies have shown that oxidative stress plays a pivotal role in the onset and progression of this disease [3], and the associated excessive generation of reactive oxygen species (ROS) has negative impacts on bone remodeling owing to osteoblast dysfunction and osteoclast activation [4,5]
We focused on the relationship between the anti-inflammatory effect of polyphenol compounds as well as their osteoporosis-alleviating effects
Summary
The World Health Organization (WHO) has defined osteoporosis as a disease characterized by low bone mass and bone tissue microarchitectural deterioration that leads to enhanced bone fragility and a consequent increase in fracture risk [1]. It is expected that polyphenols, with antioxidative and anti-inflammatory potential, would serve as a safe and suitable remedy for postmenopausal osteoporosis. This is consistent with epidemiological reports showing that dietary flavonoids, which are bioactive polyphenols, ameliorate bone health [9,10]. Upon ROS generation by polyphenols, cells could activate the Nrf pathway independently of polyphenols’ antioxidant activity. This idea drove us to focus on in vivo studies of polyphenols. The screening was further narrowed down to studies that were conducted within the last two decades (2002–2021) in which polyphenols were orally administered
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