Puerarin Attenuates Osteoarthritis via Upregulating AMP-Activated Protein Kinase/Proliferator-Activated Receptor-γ Coactivator-1 Signaling Pathway in Osteoarthritis Rats

Abstract

Background/Aims: Osteoarthritis is the most common degenerative joint disease and causes major pain and disability in adults. It has been reported that mitochondrial dysfunction in chondrocytes was associated with osteoarthritis. Puerarin has multiple effects including restoring mitochondrial function. In this study, the potential effects of puerarin on osteoarthritis and osteoarthritis associated mitochondrial dysfunctions were evaluated. Methods: Osteoarthritis rats were treated with puerarin and the severity of osteoarthritis and cartilage damages was evaluated. The mitochondrial biogenesis and functions were analyzed by measuring related proteins expression, mitochondrial DNA content, ATP production, and oxygen consumption. The dependence of AMP-activated protein kinase (AMPK) pathway on puerarin-regulated mitochondrial function was analyzed by applying AMPK inhibitor Compound C. Results: Puerarin treatment alleviated mechanical hyperalgesia and cartilage damage in osteoarthritis rats. Puerarin increased mitochondrial biogenesis and attenuated mitochondrial dysfunctions in osteoarthritis rats. AMPK inhibitor Compound C abolished puerarin’s effects. Conclusion: Puerarin attenuates osteoarthritis by upregulating the AMPK/proliferator-activated receptor-γ coactivator signaling pathway in osteoarthritis rats.

The Protective Effect of Dietary Administration of Puerarin on Canine Osteoarthritis Model With Anterior Cruciate Ligament Transected

“…The dogs were ranged by weight and randomly divided into control group (sham operation, n = 4) and model group (ACLT surgery, n = 12) to which the animal care personnel were blinded. The model group is divided into 3 subgroups (n = 4 in each group): OA group: untreated; celecoxib group: 200 mg/day celecoxib [32] (P zer Pharmaceutical, New York, USA) treated canine OA (positive control); Puerarin group: puerarin (Chengdu Mansite Biological Technology, Chengdu, China) 20 mg/kg/day to treat canine OA; The dosage of puerarin was determined according to previous studies [16,17] and according to FDA guidelines [45]. The Laboratory Animal Welfare and Ethics Committee of Northeast Agricultural University (#NEAU-2017-06-0384-12) approved the experimental design and animal surgery procedures in this study.…”

“…Puerarin in collagen matrix has the effect of increasing new bone formation locally and can be used for bone grafting or for bone induction [15]. Previous studies have shown that in rat and mouse OA models, puerarin can effectively inhibit in ammation and improve OA [16,17]. However, the effect of puerarin on canine OA has not been evaluated.…”

“…It can reduce mechanical hyperalgesia and cartilage damage in OA rats [16], increase the proliferation of cartilage cells in mice and reduce the recruitment of in ammatory monocytes [17]. We evaluated the effects of puerarin in a canine OA model for the rst time.…”

Recent advance in treatment of osteoarthritis by bioactive components from herbal medicine

“…Mitochondrial dysfunction in chondrocytes is associated with OA, and induces oxidative stress [88]. Puerarin [88] and quercetin [84] may attenuate mitochondrial dysfunction in OA rats. Subsequently, oxidative stress induces endoplasmic reticulum stress in OA, and quercetin may also repress this process by activating the sirtuin1/AMPK signaling pathway [21].…”

“…Resveratrol [ 61 ], tetramethylpyrazine [ 13 , 70 ], celastrol [ 54 ], isofraxidin [ 33 , 34 ], paeonol [ 56 ], shikonin [ 35 ], coptisine [ 44 ], piperine [ 45 ], butein [ 46 ], genistein [ 58 ], kaempferol [ 47 ], licochalcone A [ 36 ], honokiol [ 50 ], 2, 3, 5, 4′-tetrahydroxystilbene-2-O-β-d-glucoside [ 60 ], compound K [ 37 ], geniposide [ 31 ], emodin [ 38 ], and curcumin [ 65 ] may reverse the abnormal expression of these indexes. Mitochondrial dysfunction in chondrocytes is associated with OA, and induces oxidative stress [ 88 ]. Puerarin [ 88 ] and quercetin [ 84 ] may attenuate mitochondrial dysfunction in OA rats.…”