Osteoarthritis (OA) is one of the most common diseases in the orthopedics department [1]. It primarily manifests as articular cartilage subchondral sclerosis, articular cartilage wear, and synovitis [2]. Due to the increase in life expectancy of humans, the aging process of the population is accelerating, and the incidence rate of OA is increasing year by year [3]. Although studies have indicated that OA is associated with numerous risk factors, including obesity, endocrine disorders, age and etc [4], the exact etiology and pathogenesis of OA are yet unidentified.

Recent studies have found that chondrocytes and synoviocytes secrete pro-inflammatory cytokine interleukin-1 (IL-1) in the local inflammatory response [5]. IL-1β is essential in the occurrence and development of OA [6]. As a result of excess IL-1β, chondrocytes are induced to cause an inflammatory reaction and matrix catabolism by accelerating the degradation of ECM and causing overproduction of pro-inflammatory factors and catabolic chemicals, including prostaglandin E2 (PGE2) and nitric oxide (no), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), thrombin sensitive protein motifs (ADAMTS), matrix metalloproteinases (MMPs) [7], [8]. Looking for inhibition (IL)-1β has become a critical component of OA treatment.

As a key regulator of cellular energy, AMP-activated protein kinase (AMPK) coordinates multiple pathways to maintain energy homeostasis [9]. SIRT1 (Sirtuin 1), a NAD-dependent nuclear histone deacetylase, has been shown to have a positive impact on antisenescence, anti-inflammation, and reduction of oxidative stress damage [10], [11], [12]. Many studies have shown that AMPK upregulates the protein expression of SIRT1 under pathological conditions, which in turn inhibits inflammation [13], [14]. SIRT1, a downstream protein of the AMPK signalling pathway, also inhibits NF-κB activity by deacetylating P65 at the Lys310 (K310) site to mediate inflammatory responses in vivo [15]. Nuclear factor-kB (NF-kB) is a significant nuclear transcription factor that plays a role in the body’s inflammatory reaction, such as apoptosis, and so on [16]. It is an important link in the occurrence and development of OA [17]. When NF-kB is activated, a series of inflammatory events occur, resulting in the phosphorylation and ubiquitination of iκBα, which in turn leads to the translocation of P65 into the nucleus [18]. Feng et al. reported that sesamol inhibited microglia-mediated inflammation by modulating the AMPK/SIRT1/NF-κB signalling pathway, thereby attenuating spinal cord injury in mice [19]. Metformin attenuates neuroinflammation induced after intraventricular haemorrhage (IVH) by modulating the AMPK/SIRT1/NF-κB pathway [20]. Thus, pharmacological activation of the AMPK/SIRT1/NF-κB signalling pathway may offer a potential therapeutic option for osteoarthritis.

In the field of drug research and development, natural products have emerged as a hot spot. They consist of rich sources and varied structures. Various natural compounds possess anti-inflammatory or anti-oxidant effects in vitro and in vivo [21], [22]. Cathelicidin-BF (BF-30) is a natural polypeptide isolated and purified from the venom of snake Bungarus fasciatus [23]. It has an amphiphilic α-helical conformation secondary structure and shows significant anti-inflammatory, anti-oxidative stress and anti-microbial and other pharmacological activities [24]. Liu et al. found that BF-30 could effectively prevent streptozotocin (STZ)-induced diabetic kidney injury by inhibiting inflammation and oxidative stress in renal tissues through activating the AMPK pathway [25]. In addition, BF-30 effectively reduces inflammation in colitis by modulating the NF-κB signalling pathway [26]. These findings suggest that BF-30 has potential efficacy in the treatment of OA. However, there are no studies on the effectiveness of BF-30 in the treatment of OA. This study confirmed that BF-30 eliminated inflammation and extracellular matrix catabolism by regulating the AMPK/SIRT1/NF-κB signalling pathway and may be used as a drug to ameliorate the progression of OA.