Aflapin(®) is a novel synergistic composition derived from Boswellia serrata gum resin (Indian Patent Application No. 2229/CHE/2008). Aflapin is more efficacious as an anti-inflammatory agent compared to the existing Boswellia products, 5-Loxin(®) and traditional 65% Boswellia extract. A 30-day, double-blind, randomized, placebo-controlled study was conducted to validate the efficacy of Aflapin(®) in the management of clinical symptoms of osteoarthritis (OA) of the knee (Clinical trial registration number: ISRCTN69643551). Sixty eligible OA subjects selected through screening were included in the study. The subjects received either 100 mg (n=30) of Aflapin(®) or placebo (n=30) daily for 30 days. Each subject 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 5, 15 and 30. A series of biochemical tests in serum, urine and hematological parameters established the safety of Aflapin. The observations suggest that Aflapin conferred clinically and statistically significant improvements in pain scores and physical function scores in OA subjects. Aflapin provided significant improvements in pain score and functional ability in as early as 5 days of treatment. In conclusion, our observations suggest that Aflapin is a safe, fast acting and effective alternative intervention in the management of OA.

Int J Med Sci. 2011;8(7):615-22.
PMID: 22022214 [PubMed - as supplied by publisher]

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.

Int J Med Sci. 2010;7(6):366-77.
PMID: 21060724 [PubMed - indexed for MEDLINE]

INTRODUCTION: 5-Loxin is a novel Boswellia serrata extract enriched with 30% 3-O-acetyl-11-keto-beta-boswellic acid (AKBA), which exhibits potential anti-inflammatory properties by inhibiting the 5-lipoxygenase enzyme. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the efficacy and safety of 5-Loxin in the treatment of osteoarthritis (OA) of the knee.

METHODS: Seventy-five OA patients were included in the study. The patients received either 100 mg (n = 25) or 250 mg (n = 25) of 5-Loxin daily or a placebo (n = 25) 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. Additionally, the cartilage degrading enzyme matrix metalloproteinase-3 was also evaluated in synovial fluid from OA patients. Measurement of a battery of biochemical parameters in serum and haematological parameters, and urine analysis were performed to evaluate the safety of 5-Loxin in OA patients.

RESULTS: Seventy patients completed the study. At the end of the study, both doses of 5-Loxin conferred clinically and statistically significant improvements in pain scores and physical function scores in OA patients. Interestingly, significant improvements in pain score and functional ability were recorded in the treatment group supplemented with 250 mg 5-Loxin as early as 7 days after the start of treatment. Corroborating the improvements in pain scores in treatment groups, we also noted significant reduction in synovial fluid matrix metalloproteinase-3. In comparison with placebo, the safety parameters were almost unchanged in the treatment groups.

CONCLUSION: 5-Loxin reduces pain and improves physical functioning significantly in OA patients; and it is safe for human consumption. 5-Loxin may exert its beneficial effects by controlling inflammatory responses through reducing proinflammatory modulators, and it may improve joint health by reducing the enzymatic degradation of cartilage in OA patients.

TRIAL REGISTRATION: (Clinical trial registration number: ISRCTN05212803.).

Arthritis Res Ther. 2008;10(4):R85.
PMID: 18667054 [PubMed - indexed for MEDLINE]

Orthopedics. 2007 Aug;30(8):624-9; quiz 630-1.
PMID: 17727018 [PubMed - indexed for MEDLINE]

Treatment with herbal medicines is very popular in Europe. In order to get information on the evidence of effectiveness of oral herbal medicines in the treatment of pain in the joints or lower back, OVID(MEDLINE), PUBMED and COCHRANE COLLABORATION LIBRARY were searched back to 1985 for systematic reviews. The level of evidence of effectiveness was defined as strong - at least two confirmatory studies demonstrating a clinical relevant effect, moderate - one confirmatory study with a clinical relevant effect and/or multiple exploratory studies of good quality; otherwise the evidence was insufficient or conflicting in the case of inconsistent findings. Fifteen systematic reviews were identified. The evidence of effectiveness was strong for a proprietary unsaponifiable avocado soybean fraction and Harpagophytum preparations containing > 50 mg harpagoside in the daily dosage, moderate for ginger and a proprietary rose hip and seed powder, insufficient for Boswellia serrata gum resin and other herbal preparations and inconsistent for a proprietary willow bark extract. Further rigorous studies are required to confirm the usefulness of herbal medicines in the treatment of osteoarthritic complaints and chronic low back pain in order to enable acceptance of the herbal medicines into the treatment guidelines.

Phytother Res. 2007 Jul;21(7):675-83.
PMID: 17444576 [PubMed - indexed for MEDLINE]

Arthritis, an inflammation of the joints, is usually a chronic disease that results from dysregulation of pro-inflammatory cytokines (e.g. tumour necrosis factor and interleukin-1beta) and pro-inflammatory enzymes that mediate the production of prostaglandins (e.g. cyclooxygenase-2) and leukotrienes (e.g. lipooxygenase), together with the expression of adhesion molecules and matrix metalloproteinases, and hyperproliferation of synovial fibroblasts. All of these factors are regulated by the activation of the transcription factor nuclear factor-kappaB. Thus, agents that suppress the expression of tumour necrosis factor-alpha, interleukin-1beta, cyclooxygenase-2, lipooxygenase, matrix metalloproteinases or adhesion molecules, or suppress the activation of NF-kappaB, all have potential for the treatment of arthritis. Numerous agents derived from plants can suppress these cell signaling intermediates, including curcumin (from turmeric), resveratrol (red grapes, cranberries and peanuts), tea polyphenols, genistein (soy), quercetin (onions), silymarin (artichoke), guggulsterone (guggul), boswellic acid (salai guggul) and withanolides (ashwagandha). Indeed, several preclinical and clinical studies suggest that these agents have potential for arthritis treatment. Although gold compounds are no longer employed for the treatment of arthritis, the large number of inexpensive natural products that can modulate inflammatory responses, but lack side effects, constitute 'goldmines' for the treatment of arthritis.

Curr Opin Pharmacol. 2007 Jun;7(3):344-51.
PMID: 17475558 [PubMed - indexed for MEDLINE]

BACKGROUND: The ancient Indian (Asian) Ayurvedic medicinal system uses herbomineral drugs to treat arthritis. Despite centuries of use, very few have been tested by drug trials. RA-11 (ARTREX, MENDAR), a standardized multiplant Ayurvedic drug (Withania somnifera, Boswellia serrata, Zingiber officinale, and Curcuma longa) is currently used to treat arthritis.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of RA-11 in patients with symptomatic osteoarthritis (OA) of the knees.

METHODS: A total of 358 patients with chronic knee pain were screened free-of-cost in "arthritis camps" in an Indian metropolis. Ninety patients with primary OA of the knees (ACR classification; Arthritis Rheum 1986;29:1039-1049) were found eligible (postanalgesic washout pain visual analog score [VAS] > or =40 mm in either or both knees on body weight-bearing activities) to enroll into a randomized, double-blind, placebo-controlled, parallel efficacy, single-center, 32-week drug trial (80% power to detect 25% difference, P = 0.05, 2-sided). Concurrent analgesics/nonsteroidal antiinflammatory drugs and steroids in any form were not allowed. Lifestyle and/or dietary restrictions, as per routine Ayurveda practices, were not imposed. Pain VAS (maximum pain in each knee recorded by the patient during the preceding 48 hours) and modified WOMAC (Western Ontario McMaster University OA Index, Likert scale, version 3.0) were the primary efficacy variables. The WOMAC section on "physical function difficulty" was modified for Indian use and validated before the trial. Routine laboratory testing was primarily done to monitor drug safety. At baseline, the groups (active = 45, placebo = 45) were well matched for several measures (mean pain VAS: active = 6.17; placebo = 6.5).

RESULTS: 1) Efficacy: Compared with placebo, the mean reduction in pain VAS at week 16 (active = 2.7, placebo = 1.3) and week 32 (active = 2.8, placebo = 1.8) in the active group was significantly (P <0.05, analysis of variance [ANOVA]) better. Similarly, the improvement in the WOMAC scores at week 16 and week 32 were also significantly superior (P <0.01, ANOVA) in the active group. 2) Safety: Both the groups reported mild adverse events (AE) without any significant difference. 3) Withdrawals: Twenty-eight patients were discontinued. None reported drug-related toxicity. The majority failed follow up/compliance. No differences were observed between the groups.

CONCLUSION: This controlled drug trial demonstrates the potential efficacy and safety of RA- 11 in the symptomatic treatment of OA knees over 32 weeks of therapy.

J Clin Rheumatol. 2004 Oct;10(5):236-45.
PMID: 17043520 [PubMed - as supplied by publisher]

An open multi-centre veterinary clinical trial, comparing conditions before and after treatment with a herbal dietary supplement consisting of a natural resin extract of Boswellia serrata, was conducted by 10 practicing veterinarians in Switzerland. This traditional plant-based supplement is known for its anti-rheumatic and anti-inflammatory properties. 29 dogs with manifestations of chronic joint and spinal disease were enrolled. Osteoarthritis and degenerative conditions were confirmed radiologically in 25 of 29 cases. The resin extract (BSB108, product of Bogar AG) was administered with the regular food at a dose of 400 mg/10 kg body weight once daily for 6 weeks. Already after two weeks of treatment, an overall efficacy of the dietary supplement was evident in 71% of 24 eligible dogs. A statistically significant reduction of severity and resolution of typical clinical signs in individual animals, such as intermittent lameness, local pain and stiff gait, were reported after 6 weeks. Effects of external factors that aggravate lameness, such as "lameness when moving" and "lameness after a long rest" diminished gradually. In 5 dogs, reversible brief episodes of diarrhea and flatulence occurred, but only once was a relationship to the study preparation suspected. Because quality and stability of the resin extract were ensured, these data suggest that a standardized preparation can be recommended as a herbal dietary supplement providing symptomatic support in canine osteoarthritic disease.

Schweiz Arch Tierheilkd. 2004 Feb;146(2):71-9.
PMID: 14994484 [PubMed - indexed for MEDLINE]

Osteoarthritis is a common, chronic, progressive, skeletal, degenerative disorder, which commonly affects the knee joint. Boswellia serrata tree is commonly found in India. The therapeutic value of its gum (guggulu) has been known. It posses good anti-inflammatory, anti-arthritic and analgesic activity. A randomized double blind placebo controlled crossover study was conducted to assess the efficacy, safety and tolerability of Boswellia serrata Extract (BSE) in 30 patients of osteoarthritis of knee, 15 each receiving active drug or placebo for eight weeks. After the first intervention, washout was given and then the groups were crossed over to receive the opposite intervention for eight weeks. All patients receiving drug treatment reported decrease in knee pain, increased knee flexion and increased walking distance. The frequency of swelling in the knee joint was decreased. Radiologically there was no change. The observed differences between drug treated and placebo being statistically significant, are clinically relevant. BSE was well tolerated by the subjects except for minor gastrointestinal ADRs. BSE is recommended in the patients of osteoarthritis of the knee with possible therapeutic use in other arthritis.

Phytomedicine. 2003 Jan;10(1):3-7.
PMID: 12622457 [PubMed - indexed for MEDLINE]

BACKGROUND: Leukotrienes and prostaglandines are important mediators of inflammation. While prostaglandine synthesis can be influenced by NSAIDs therapeutical approaches to the 5-lipoxygenase pathway are rare. Resinous extracts of Boswellia serrata (H15, indish incense), known from traditional ayurvedic medicine, decrease leukotriene synthesis in vitro. Case reports suggest a clinical role for that drug.

METHODS: Outpatients with active RA have been enrolled into a multicenter controlled trial. Patients received 9 tablets of active drug (3600 mg) or placebo daily in addition to their previous therapy. Doses of NSAIDs could be adjusted on demand. Efficacy parameters, Ritchies Index for swelling and pain, ESR, CRP, pain on VAS and NSAID dose were documented at baseline and 6 and 12 weeks after initiation. Mean values and medians were calculated to compare the groups for significant or clinically relevant change from baseline or difference between both groups at any time point of observation.

RESULTS: A total of 78 patients were recruited in 4 centers, the data have been published in abstract form. Only 37 patients (verum 18, placebo 19), enrolled in Ratingen were available for detailed efficacy and safety analysis. All evaluations in these patients were performed by one investigator (G.H.). There was no subjective, clinical or laboratory parameter showing a significant or clinically relevant change from baseline or difference between both groups at any time point of observation. The mean NSAID dose reduction reached levels of 5.8% (H15) and 3.1% (placebo). One patient in each group showed a good response in all parameters but 4 patients in each group worsened. The others showed no alteration of their disease.

CONCLUSION: Treatment with H15 showed no measurable efficacy. Controlled studies including a greater patient population are necessary to confirm or reject our results.

Z Rheumatol. 1998 Feb;57(1):11-6.
PMID: 9566100 [PubMed - indexed for MEDLINE]

The clinical efficacy of a herbomineral formulation containing roots of Withania somnifera, the stem of Boswellia serrata, rhizomes of Curcuma longa and a zinc complex (Articulin-F), was evaluated in a randomized, double-blind, placebo controlled, cross-over study in patients with osteoarthritis. After a one-month single blind run-in period, 42 patients with osteoarthritis were randomly allocated to receive either a drug treatment or a matching placebo for a period of three months. After a 15-day wash-out period the patients were transferred to the other treatment for a further period of three months. Clinical efficacy was evaluated every fortnight on the basis of severity of pain, morning stiffness, Ritchie articular index, joint score, disability score and grip strength. Other parameters like erythrocyte sedimentation rate and radiological examination were carried out on a monthly basis. Treatment with the herbomineral formulation produced a significant drop in severity of pain (P less than 0.001) and disability score (P less than 0.05). Radiological assessment, however, did not show any significant changes in both the groups. Side effects observed with this formulation did not necessitate withdrawal of treatment.

J Ethnopharmacol. 1991 May-Jun;33(1-2):91-5.
PMID: 1943180 [PubMed - indexed for MEDLINE]