An Anti‐Inflammatory Composition of <i>Boswellia serrata</i> Resin Extracts Alleviates Pain and Protects Cartilage in Monoiodoacetate‐Induced Osteoarthritis in Rats
Krishnaraju Venkata Alluri, Sreenath Kundimi, K. Sengupta, Trimurtulu Golakoti, Eswar Kumar Kilari
Abstract
The boswellic acids, the active compounds in Boswellia serrata gum resin extract, are potent anti‐inflammatory agents and are specific nonredox inhibitors of 5‐Lipoxygenase (5‐LOX). Here, we present the anti‐osteoarthritis (OA) efficacy of LI13019F1 (also known as Serratrin®), a unique composition containing the acidic and nonacidic fractions of B. serrata gum resin. This composition strongly inhibited 5‐LOX activity with the half‐maximal inhibitory concentration (IC 50 ) of 43.35 ± 4.90 μ g/mL. Also, LI13019F1 strongly inhibited the leukotriene B 4 (IC 50 , 7.80 ± 2.40 μ g/mL) and prostaglandin E 2 (IC 50 , 6.19 ± 0.52 μ g/mL) productions in human blood‐derived cells. Besides, LI13019F1 reduced TNF‐ α production with the IC 50 of 12.38 ± 0.423 μ g/mL. On average, 1, 2.5, and 5 μ g/mL doses of LI13019F1 protected 34.62, 47.66, and 62.29% SW1353 human chondrosarcoma cells from IL‐1 β induced SOX‐9 depletion, respectively. Further, a 28‐day preclinical proof‐of‐concept study evaluated the pain relief efficacy of LI13019F1 in monoiodoacetate‐ (MIA‐) induced Sprague-Dawley rats. At the end of the study, 150 and 300 mg/kg doses of LI13019F1 supplemented rats showed significant improvements (55.17 ± 5.81 g ( p < 0.05), and 66.22 ± 6.30 g ( p < 0.05), respectively, vs. MIA: 31.22 ± 7.15 g) in body‐weight‐bearing capacities. Concurrently, LI13019F1‐150 and LI13019F1‐300 rats substantially ( p < 0.05) increased the threshold of pain sensitivity to pressure (26.98 ± 2.36 and 28.06 ± 2.72‐gram force, respectively; vs. 18.63 ± 5.82 in MIA) and increased ( p < 0.05) the latent time to withdraw the paw after a thermal stimulus (23.61 ± 2.73 and 28.18 ± 1.90 sec, respectively; vs. 16.56 ± 1.22 sec. in MIA). Besides, the histological observations on Safranin‐O green stained articular cartilage revealed that LI13019F1 also prevented the MIA‐induced structural damage of the cartilage and reduced the loss of the extracellular matrix (ECM) components in the experimental rats. In conclusion, the present observations suggest that LI13019F1, a new composition of B. serrata gum resin extracts, reduces pain and protects articular cartilage from the damaging action of MIA in a rodent model.