Boswellin® PS
 
  - Patent Pending
Full Spectrum Anti-Inflammatory Bio-actives from Boswellia serrata
 
Traditional Uses of Boswellia
  • Long history of use in religious ceremonies and for perfume production and its medicinal properties have been appreciated for millennia.
  • In India, the gum resin exudates of Boswellia serrata, known in the vernacular as "Salai guggal", has been used in the Ayurvedic system of medicine in the management of several inflammatory disorders.
 
Boswellia Gum Composition
Typically the Gum Oleoresin of Boswellia is reported to consists of:
    • Sesquiterpenoid essential oils (8-12%),
    • Polysaccharides (45-60%),
    • Higher terpenoids, including Boswellic acids (25–35%).

    Boswellin® PS is obtained from the gum exudate of Boswellia serrata trees commonly known as Frankincense.
 
Boswellin® PS
Boswellin® PS is standardized to contain:
    • AKBBA 10% (MIN)
    • Total Identified Boswellic Acids 20% (MIN)
    • Total Organic Acids 35% (MIN)

    In addition to the active Boswellic acids, Boswellin® PS also contains Polysal which contributes to its immediate anti-inflammatory action.
 
Salient Features of Boswellin® PS
  • 100% Natural
  • No Excipients
  • No Preservatives
  • Enhanced solubility in Water
  • Enhanced AKBBA content than regular Boswellin®
  • Contains Full-Spectrum Anti-Inflammatory Bio-actives from Boswellia Gum
  • Standardized and contains both the hydrophilic and lipophilic fractions of Boswellia Gum
  • Enhanced Safety
 
Proposed Mechanism of Action
  • Boswellin® PS contains the Boswellic acids and Polysal, both of which provide anti-inflammatory action.
  • The water-soluble Polysal initiates and supports the anti-inflammatory activity, while the lipid-soluble Boswellic acids help to provide a sustained action.
Boswellin® - Chemistry
The FOUR major identified pentacyclic triterpenoids in Boswellin® are…
    • β -Boswellic acid
    • Acetyl- β -Boswellic acid
    • 11-keto- β -Boswellic acid
    • Acetyl -11 –keto –β -Boswellic acid
 
Chemistry of Boswellic Acids

β-Boswellic Acid

Acetyl-β-Boswellic Acid

11-Keto-β-Boswellic Acid

Acetyl 11-Keto-β-Boswellic Acid
 
Polysal - Chemistry
  • Polysal has been reported to contain mainly neutral sugars as Polysaccharides.
  • The polysaccharide is reported to primarily consist of galactose, arabinose and D-glucuronic acid.
  • 4-o-methyl-glucuronoarabino-galactan has been identified as one of the polysaccharides.
  • The polysaccharide has a molecular weight of 5.1 – 5.6 X 105 against dextran standards.
  • The polysaccharide has an Optical Rotation [α]D – 10.50 and contains 64% to 69% neutral sugars.
Mechanism of Action
 
Arachidonic Acid Pathway and Action of Boswellic Acids
 
A. Inhibition of Leukotrienes Formation
  • Leukotrienes are fatty acids which are formed from arachidonic acid by an enzyme called Lipoxygenase.
  • Function of Leukotrienes is to sustain the inflammatory reactions in the body by acting as chemo attractants for leucocytes that are the reservoirs of pro-inflammatory cytokines like TNFα.
  • Boswellic acids are reported to be non competitive inhibitors of 5-Lipoxygenase enzyme.
  • AKBBA has been shown to be the most potent inhibitor of 5-Lipoxygenase enzyme.
Boswellic Acids in Inhibiting the Enzyme 5-lipoxygenase
 
B. Inhibition of Human Leukocyte Elastase (HLE)
  • HLE is a serine protease and play an important role in several inflammatory diseases like
    • Cystic fibrosis
    • Pulmonary emphysema
    • Rheumatic arthritis
    • Chronic bronchitis
  • Boswellic acids block the HLE activity

          Dual inhibition of HLE and 5- Lipoxygenase enzyme is unique to the Boswellic acids

 
Anti-inflammatory Potential of Boswellia Extract and Polysal
  • Polysal showed a dose dependent anti-inflammatory potential, similar to the Boswellic acids.
  • The Polysal and Boswellic acids when combined exhibited an enhanced effect with regard to its anti-inflammatory potential.
 
Pre-Clinical Experimental Study
Studies were carried out in 3 phases
  • In vitro - TNFα estimation in murine neutrophils
  • In vivo - TNFα, IL-1β and inducible Nitric oxide (NO) estimation in male Swiss Albino mice
  • In vivo study in Wistar Albino arthritis induced rats
    • Developing arthritis (Prophylactic effect)
    • Established arthritis (Therapeutic effect)
      • Endpoints
        • Paw oedema
        • Tissue cytokines
          1. LTB4
          2. TNFα
          3. PGE2
 
In vitro - TNFα estimation in murine neutrophils
Anti-inflammatory Potential of Boswellin® and Boswellin® PS (in vitro)
  • LPS (Lipopolysaccharide) (E. Coli, Sigma Aldrich, India) endotoxin is an important triggering factor for systemic inflammatory response.
  • TNF-α cytokine is a major pro-inflammatory cytokine and plays a very important role in the pathogenesis of septic shock induced by LPS.
  • Anti-inflammatory potential of Boswellin® and Boswellin® PS was evaluated by Flow Cytometer studies in murine neutrophils.

Intracellular in vitro TNF-α estimation in Murine Neutrophils

 
In vivo - TNFα, IL-1β & inducible Nitric oxide (NO) estimation in male Swiss Albino mice
Importance of the Inflammatory Markers-1
  • TNF – α (tumor necrosis factor-alpha) is a cytokine involved in systemic inflammation and stimulates the acute phase reaction.
  • Dysregulation of TNF production has been implicated in a variety of human diseases including cancer.

Extracellular in vivo TNF-α Estimation in Serum

 

Importance of the Inflammatory Markers-2

  • IL-1β (interleukin-1 beta) is one of the most potent pro‐inflammatory cytokines involved both in physiological immune responses and in the development of various immunopathological disorders.
  • Checking IL-1β levels is useful in monitoring and diagnosis of various diseases including inflammatory, immunological and bone diseases.

Extracellular in vivo IL-1 β Estimation in Serum

Importance of the Inflammatory Markers-3
  • Appropriate levels of Nitric Oxide production are important in protecting an organ such as the liver from ischemic damage.
  • However sustained levels of NO production result in direct tissue toxicity and contribute to the vascular collapse.
  • Chronic expression of NO is associated with various carcinomas and inflammatory conditions including juvenile diabetes, multiple sclerosis, arthritis and ulcerative colitis.
Extracellular in vivo IL-1 β Estimation in Serum
 

In vivo study in Wistar Albino arthritis induced rats
    Developing arthritis (Prophylactic effect)
    Established arthritis (Therapeutic effect)

Boswellic Acids compared with Polysal
  • Polysal and Boswellic acids were compared and evaluated for their anti-arthritic potential in male wistar rats.
  • Inhibition of oedema was studied on adjuvant induced developing and developed arthritic groups of animals.
Boswellic Acids compared with Polysal Anti-Arthritic Potential
 
Anti-arthritic activity (Prophylactic) of test samples in Mycobacterium tuberculosis induced inflammatory arthritis in rats (injected paw)

p value * < 0.01; **< 0.001;  (ASA: Acetylsalicylic acid (standard)-100mg/kg; BA: Boswellia Regular
POLY: Polysal; BOS.PS: Boswellin® PS (Polysal + Boswellic acid + AKBBA-10%)

 
Anti-arthritic activity (Therapeutic) of test samples (effective dose) in Mycobacterium tuberculosis induced established inflammatory arthritis in rats (injected paw)

p value * < 0.01; **< 0.001;  ASA: Acetylsalicylic acid (standard)-100mg/kg; BA: Boswellia Regular
POLY: Polysal; BOS.PS: Boswellin® PS (Polysal + Boswellic acid + AKBBA-10%)

 
Expression of LTB4 in supernatant from arthritic paw tissue homogenate in Mycobacterium tuberculosis induced inflammatory arthritis in rats treated with different test samples at graded dose levels
p value * < 0.01; **< 0.001; ASA: Acetylsalicylic acid (standard)-100mg/kg; BA: Boswellia Regular
POLY: Polysal; BOS.PS: Boswellin® PS (Polysal + Boswellic acid + AKBBA-10%)
 
Expression of TNF-alpha in supernatant from arthritic paw tissue homogenate in Mycobacterium tuberculosis induced inflammatory arthritis in rats treated with different test samples at graded dose levels
p value * < 0.01; **< 0.001; (ASA: Acetylsalicylic acid (standard)-100mg/kg; BA: Boswellia Regular
POLY: Polysal; BOS.PS: Boswellin® PS (Polysal + Boswellic acid + AKBBA-10%)
 
Expression of PGE2 in supernatant from arthritic paw tissue homogenate in Mycobacterium tuberculosis induced inflammatory arthritis in rats treated with different test samples at graded dose levels

p value * < 0.01; **< 0.001;  ASA: Acetylsalicylic acid (standard)-100mg/kg; BA: Boswellia Regular
POLY: Polysal; BOS.PS: Boswellin® PS (Polysal + Boswellic acid + AKBBA-10%)

 
Conclusion
  • The significant dose related inhibition of TNF-α in both in vitro and in vivo pre-clinical test models was observed in the isolated murine neutrophils.
  • Boswellin® PS was shown to have most significant dose related anti-arthritic activity in Mycobacterium tuberculosis induced developing adjuvant arthritis test in rats which was comparatively more than the other test materials.
  • Boswellin® PS showed the significant inhibition of absolute oedema by different test materials in Mycobacterium tuberculosis induced established adjuvant arthritis.
  • Boswellin® PS may be
    • partially immunosuppressive in nature and
    • partially it may be due to the inhibition of pro-inflammatory cytokines and mediators.
 
Solubility
 
Toxicity
  • Both Boswellic acids and Polysal were found to have good safety profile.
  • Acute Oral Toxicity (LD0) [OECD Guideline] for Boswellic Acids was found to be 2000mg/kg b.w.
  • Acute Oral Toxicity (LD0) [OECD Guideline] for Polysal was found to be 2000mg/kg b.w.
 
Dosage
  • Boswellin® PS can be suggested at a dosage of up to 200mg, 2 times a day.
 
Applications
  • Boswellin® PS can find potential use in management of various inflammatory disorders.
    • Rheumatoid arthritis
    • Osteoarthritis
    • Chronic colitis
    • Ulcerative colitis
    • Crohn's disease
    • Bronchial asthma
    • Peritumoral brain edemas
 
 
© Sabinsa Corporation 2010