Low Dose, High-AKBA Boswellia for Rheumatoid Arthritis

Bones, Joints, Muscles & Tendons

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Rheumatoid arthritis (RA) affects over 1.5 million Americans. To fight the pain, many people turn to non-steroidal anti-inflammatory drugs (NSAIDs). But NSAIDs do nothing for the 5-lipoxygenase pathway, a key factor in RA, and instead cause liver and stomach damage – and in some cases, hospitalization.

This study found that a special extract of Boswellia serrata, (BOS-10), was significantly better absorbed than standard extracts and performed much better at reducing inflammation at low dosages. Additionally, it prevented the liver damage caused by methotrexate used in an animal model of arthritis and made the drug more effective.

The key to this extract’s success is that it delivers at least 10 percent acetyl-11-keto-B-boswellic acid (AKBA), a beneficial compound of boswellia that fights inflammation along the 5-LOX pathway. Standard extracts tend to be low on AKBA, generally averaging only about 2 percent by comparison.

Compared to standard boswellia, the high-AKBA form scored remarkably well in critical ways:

• Absorption: 5 mg of 10% AKBA was 8 times better absorbed then 40 mg of 2% AKBA
• Inflammation: 40 mg of 2% AKBA boswellia reduced inflammation by 40% while just 5 mg of 10% AKBA reduced inflammation by 44%; boosting that amount to 40 mg of 10% AKBA reduced inflammation by 75%

Additionally, animals treated with the drug methotrexate or 10% AKBA boswellia alone had about a 50% reduction in inflammatory symptoms. Combining the two treatments reduced inflammation by 63%, while boswellia also protected the liver from the damaging effects of the drug.

In the future, boswellia with 10 percent AKBA may be used as a first line of treatment for rheumatoid arthritis, or as a complementary treatment with conventional drugs, making them more effective and causing less damage or side effects.

Abstract:

Banji D, Bandi OJ, Rashida S, Alshaharani S, Alqahtani SS. Bioavailability, anti-inflammatory and anti-arthritic effect of Acetyl Keto Boswellic acid and its combination with methotrexate in an arthritic animal model. J Ethnopharmacol. 2022;292:115200.

Ethnopharmacological relevance: Rheumatoid arthritis is one of the most common disabling chronic progressive autoimmune diseases affecting the adult world population. Boswellia serrata has been a known anti-inflammatory agent since ancient times. Therefore, research on Boswellia extract based on Acetyl Keto Boswellic Acid (AKBA) content evaluating its efficacy and safety is necessary. The study aimed to find a suitable Boswellia extract rich in AKBA to evaluate its bioavailability, anti-inflammatory, and anti-arthritic effect. In addition, the synergistic action of AKBA extract with methotrexate (MTX) was also assessed on an animal model. 

Materials and methods: Oral bioavailability of AKBA and the anti-inflammatory activity of 10% AKBA (5, 10, 20, 40 mg/kg b.w) was assessed and compared with 2% AKBA (40 mg/kg) and diclofenac (10 mg/kg). The effect of 10% AKBA at 20 mg/kg and 40 mg/kg was evaluated in the FCA induced arthritis animal model alone and combined with methotrexate (MTX) at 2 mg/kg b.w. Subplantar injection of FCA produced edema within a few hours with progressive arthritis by the 9th day after injection. All the treatments were initiated from the 10th day until the 45th day. Oral administration of 10% AKBA was done daily and MTX by intraperitoneal route once a week from day 10 to day 45. Paw volume, erythrocyte sedimentation rate (ESR), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), total bilirubin, oxidative markers (superoxide dismutase (SOD) levels, malondialdehyde (MDA), total proteins and liver histopathology were examined. 

Results: 10% AKBA provided 8.48-fold, 24.22-fold, 47.36-fold, and 110.53-fold higher AUC (0-α) of AKBA at 5 mg/kg, 10 mg/kg, 20 mg/kg and 40 mg/kg, respectively compared to 2% AKBA at 40 mg/kg. Percentage paw edema inhibition of 10% AKBA at 20 mg/kg and 40 mg/kg were significantly higher than 2% regular AKBA (40 mg/kg) and diclofenac (10 mg/kg). 10% AKBA at a dose of 20 and 40 mg/kg significantly reduced ESR compared with FCA treated group. A combination of methotrexate with 10% AKBA showed the highest reduction in ESR. 10% AKBA at both dose levels significantly reduced hepatic marker enzymes and total bilirubin levels. Treatment with 10% AKBA showed a significant increase in total proteins, antioxidant enzymes and a decrease in malondialdehyde levels. Similarly, 10% AKBA protected the hepatocytes compared with the FCA and FCA + MTX treated group. 10% AKBA was capable of significantly minimizing FCA and FCA + MTX induced changes. 

Conclusion: Anti-inflammatory activity of AKBA due to inhibition of lipoxygenase (LOX) enzymes supports the use of AKBA in inflammatory disorders. Combination therapy of 10% AKBA with MTX is effective in inhibiting arthritis and circumventing hepatotoxicity produced by MTX in arthritic animals.