Xanthohumol alleviates palmitate-induced inflammation and prevents osteoarthritis progression by attenuating mitochondria dysfunction/NLRP3 inflammasome axis

Weichao Sun; Jiaji Yue; Tianhao Xu; Yinxing Cui; Dixi Huang; Houyin Shi; Jianyi Xiong; Wei Sun; Qian Yi

doi:10.1016/j.heliyon.2023.e21282

Xanthohumol alleviates palmitate-induced inflammation and prevents osteoarthritis progression by attenuating mitochondria dysfunction/NLRP3 inflammasome axis

Heliyon. 2023 Oct 27;9(11):e21282. doi: 10.1016/j.heliyon.2023.e21282. eCollection 2023 Nov.

Authors

Weichao Sun^{1

2}, Jiaji Yue¹, Tianhao Xu^{3

4}, Yinxing Cui^{1

5}, Dixi Huang^{1

5}, Houyin Shi⁶, Jianyi Xiong¹, Wei Sun¹, Qian Yi^{5

4}

Affiliations

¹ Department of Orthopedics, Shenzhen Second People's Hospital (The First Affiliated Hospital of Shenzhen University), Shenzhen, Guangdong, 518035, China.
² The Central Laboratory, Shenzhen Second People's Hospital (The First Affiliated Hospital of Shenzhen University), Shenzhen, Guangdong 518035, China.
³ Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, China.
⁴ Laboratory of Anesthesia and Organ Protection, Southwest Medical University, Luzhou, Sichuan, 646099, China.
⁵ Department of Physiology, School of Basic Medical Science, Southwest Medical University, Luzhou, Sichuan, 646000, China.
⁶ Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, China.

Abstract

Osteoarthritis (OA) is a prevalent chronic degenerative joint disease worldwide. Obesity has been linked to OA, and increased free fatty acid levels (e.g., palmitate) contribute to inflammatory responses and cartilage degradation. Xanthohumol (Xn), a bioactive prenylated chalcone, was shown to exhibit antioxidative, anti-inflammatory, and anti-obesity capacities in multiple diseases. However, a clear description of the preventive effects of Xn on obesity-associated OA is unavailable. This study aimed to assess the chondroprotective function of Xn on obesity-related OA. The in vitro levels of inflammatory and ECM matrix markers in human chondrocytes were assessed after the chondrocytes were treated with PA and Xn. Additionally, in vivo cartilage degeneration was assessed following oral administration of HFD and Xn. This study found that Xn treatment completely reduces the inflammation and extracellular matrix degradation caused by PA. The proposed mechanism involves AMPK signaling pathway activation by Xn, which increases mitochondrial biogenesis, attenuates mitochondrial dysfunction, and inhibits NLRP3 inflammasome and the NF-κB signaling pathway induced by PA. In summary, this study highlights that Xn could decrease inflammation reactions and the degradation of the cartilage matrix induced by PA by inhibiting the NLRP3 inflammasome and attenuating mitochondria dysfunction in human chondrocytes.

Keywords: AMPK/NF-κB signaling pathway; Mitochondria dysfunction; NLRP3 inflammasome; Osteoarthritis; Palmitate; Xanthohumol.