Comparative efficacy and tolerability of 5-Loxin and AflapinAgainst osteoarthritis of the knee: a double blind, randomized, placebo controlled clinical study

Abstract

Aflapin(®) is a novel synergistic composition derived from Boswellia serrata gum resin (Indian Patent Application No. 2229/CHE/2008). Aflapin is significantly better as an anti-inflammatory agent compared to the Boswellia extracts presently available in the market. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the comparative efficacy and tolerability of 5-Loxin(®) and Aflapin(®) in the treatment of osteoarthritis (OA) of the knee (Clinical trial registration number: ISRCTN80793440). Sixty OA subjects were included in the study. The subjects received either 100 mg (n=20) of 5-Loxin(®) or 100 mg (n=20) of Aflapin(®) or a placebo (n=20) daily for 90 days. Each patient was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne's Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 7, 30, 60 and 90. A battery of biochemical parameters in serum, urine and hematological parameters in citrated whole blood were performed to assess the safety of 5-Loxin(®) and Aflapin(®) in OA subjects. Fifty seven subjects completed the study. At the end of the study, both 5-Loxin(®) and Aflapin conferred clinically and statistically significant improvements in pain scores and physical function scores in OA subjects. Interestingly, significant improvements in pain score and functional ability were recorded as early as 7 days after initiation of the study in the treatment group supplemented with 100 mg Aflapin. Corroborating the improvements in pain scores in treatment groups, our in vitro studies provide evidences that Aflapin(®) is capable of inhibiting cartilage degrading enzyme MMP-3 and has the potential to regulate the inflammatory response by inhibiting ICAM-1. Aflapin(®) and 5-Loxin(®) reduce pain and improve physical functions significantly in OA subjects. Aflapin exhibited better efficacy compared to 5-Loxin(®). In comparison with placebo, the safety parameters were almost unchanged in the treatment groups. Hence both 5-Loxin(®) and Aflapin(®) are safe for human consumption.

Keywords: 5-Loxin®; Aflapin®; Boswellia serrata; anti-inflammation; osteoarthritis and clinical study..

Figure 1

Flow chart of the subjects who participated in the clinical trial. Evaluations of physical activity and pain scores, serum biochemistry, hematology, and urine biochemistry were done at baseline (day 0) and on days 7, 30, 60 and 90 during follow up.

Figure 2

Bar diagrams represent the mean scores of (a) visual analog scale (VAS) (a); Lequesne's Functional Index (LFI) (b); Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-pain (c); WOMAC-stiffness (d); and WOMAC-function (e) in placebo, 100 mg/ day 5-Loxin^® and 100 mg/day Aflapin^® groups, respectively. 1 to 5, represent days of evaluations such as day 0, day 7, day 30, day 60 and day 90, respectively. Each bar represents mean ± standard deviation. In comparison with corresponding baseline data, the change in scores in the treatment groups was tested for significance using Tukey's multiple comparison test; * p<0.05; ** p<0.005.

Figure 3

Aflapin and 5-Loxin inhibit matrix metalloproteinase-3 secretion from TNFα-induced human primary chondrocytes. Line diagram represents MMP-3 concentrations in the culture supernatants of chondrocytes treated with 5 ng/ml of human recombinant TNFα in presence or absence of different doses of either 5-Loxin or Aflapin as indicated. Vehicle control cultures received 0.01% DMSO. Each data point represents the mean of quadruplicate wells.

Figure 4

Aflapin and 5-Loxin inhibit TNFα-induced ICAM-1 expression on human dermal microvascular endothelial cells (HDMEC). Bar diagrams represent the ICAM-1 expression on HDMEC treated with 20ng/ml of human recombinant TNF-α in presence or absence of either 5-Loxin (4µg/ml) or Aflapin (4µg/ml) as indicated. Vehicle control cultures received 0.01% DMSO. Each experiment is done in quadruplicate wells. The results are expressed as the mean±SD of five experiments in quadruplicate wells. 5-Loxin and Aflapin significantly inhibits ICAM-1 expression induced by TNF-α (p<.01, student t-test).