Boswellia serrata Extract, 5-Loxin®, Prevents Joint Pain and Cartilage Degeneration in a Rat Model of Osteoarthritis through Inhibition of Inflammatory Responses and Restoration of Matrix Homeostasis

Abstract

Osteoarthritis (OA) is a chronic, progressive joint disease associated with pain, functional impairment, and diminished quality of life in affected individuals. At a societal level, it also has a high economic burden. Boswellia serrata has been reported to have potent anti-inflammatory, antiarthritic, and analgesic effects. The aim of this study was to explore the therapeutic potential and possible underlying mechanism of 5-Loxin®, a standardized Boswellia serrata extract, in a rat model of OA. The OA model was established by the intra-articular injection of 50 μL of monosodium iodoacetate (MIA) (60 mg/mL). 5-Loxin® was administered orally, and efficacy was evaluated through serum analysis, real-time polymerase chain reaction (PCR), histologic staining, and micro-computed tomography (micro-CT). Results indicated that administration of 5-Loxin® can relieve OA joint pain through inhibition of both inflammatory processes and cartilage degeneration. In the group of rats treated with 5-Loxin®, the suppression of inflammatory enzymes such as cyclooxygenase (COX)-2 and 5-lipoxygenase (LOX) resulted in a significant reduction in the prostaglandin (PG) E2 and leukotriene (LT) B4 levels. Moreover, 5-Loxin® ameliorated the deterioration of the main components of the articular extracellular matrix (ECM), such as glycosaminoglycans (GAGs) and aggrecan, through the downregulation of matrix metalloproteinases (MMPs). These findings suggest that 5-Loxin® may be a potential therapeutic agent for the treatment of OA.

Frankincense preparation promotes formation of inflammation-resolving lipid mediators by manipulating lipoxygenases in human innate immune cells

“…lowered anti-collagen antibodies, cartilage oligomeric matrix protein, C-reactive protein, TNF-α, IL-6, nitric oxide, PGE 2 , and COX-2 levels, along with reduction in arthritic index, paw volume, and joint inflammation ( Majeed et al, 2021 ). In our study, we achieved significant LM modulation with BSR starting at 10 up to 100 μg/mL, which are pharmacologically relevant concentrations, as BSR/5-Loxin® were efficacious when supplied at comparable or even higher doses (i.e., 40–200 μg/g) ( Majeed et al, 2021 ; Shin et al, 2022 ), as stated above. In light of the effects of BSR/5-Loxin® on inflammatory mediators and enzymes in these studies on animal diseases, it is interesting that exogenously added SPMs reduced the levels of pro-inflammatory cytokines like TNF-α and IL-6 as well as of MMPs and nitric oxide in comparable arthritis models ( Chiang and Serhan, 2020 ).…”

“…Hence, in a rat OA model, 5-Loxin® (100 and 200 μg/g body weight, p.o.) relieved OA joint pain along with suppression of PGE 2 and LTB 4 levels ( Shin et al, 2022 ). Likewise, in rats with collagen-induced arthritis, BSR (40 and 80 μg/g body weight, p.o.)…”

Osteoarthritis: Insights into Diagnosis, Pathophysiology, Therapeutic Avenues, and the Potential of Natural Extracts

“…Kimmatkar and colleagues, in their 2003 RCT, found that when compared with placebo controls, Boswellia extract was significant in decreasing knee pain and swelling [344]. This was also reflected in later studies, either in novel formulations or in combination with other extracts [345][346][347][348]. Neither of these studies, however, compared the efficacy of the extract with any common NSAID; hence, the results cannot be considered conclusive.…”

From Preclinical to Clinical Evidence: Exploring the Multiple Perspectives and Healing Power of Boswellia Serrata Roxb. Ex Colebr

“…Numerous randomized controlled studies researched the safety and efficacy of B. serrata extract in the treatment of osteoarthritis (OA) (53)(54)(55)(56)(57)(58)(59)(60).…”