Boswellic Acid

Natural Synergy

Traditional Chinese Medicine

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Summary of Research and Conclusions

Seven in-vitro studies have reported that boswellic acid inhibited proliferation and/or induced differentiation in leukemia or central nervous system cancer cell lines.54-60 In addition, cyto-toxic effects against two cancer cell lines have been observed by our research group.61 At least three animal antitumor studies have been published, which found that boswellic acids inhibited the growth of transplanted brain cancer cells and leukemia cells in rodents.62 63 64 Two human studies have also been conducted.65,66 These indicated that Boswellia extracts or bos-wellic acid could reduce brain edema or otherwise have a palliative effect in brain cancer patients.

Discussion

Frankincense is the gum resin secreted by the tree Boswellia serrata (or B. carteri). Frankincense and its close relative myrrh (Commiphora species.) have a history of use dating to ancient Egyptian civilizations 5,000 years ago.67,68 Both plants are used in Chinese herbal medicine for treating pain from trauma and other swellings. Frankincense is also applied topically to promote healing of sores. A primary active compound in frankincense is boswellic acid, which occurs naturally in both an alpha and beta form (see Figures A.65 and A.66 in Appendix A).

Numerous studies documented that boswellic acid and/or Boswellia extracts produce anti-inflammatory effects. For example, the alcohol extract of Boswellia produced anti-inflammatory effects in rats at oral doses of 50 mg/kg.69 Mitigation of chronic arthritis (including a reduction in collagen degradation) was observed at an oral dose of 100 mg/kg in rats; in this study, alcohol extracts were just slightly more effective than boswellic acid alone.70 Oral doses of 50 to 200 mg/kg of the alcohol extract reduced leukocyte migration at inflammatory sites in rats.71 Oral administration of boswellic acid at 25 to 100 mg/kg improved chronic arthritis in rabbits.72 The human equivalents to these animal doses range from about 0.73 to 3.2 grams per day.

Anti-inflammatory effects have also been observed in human studies. In arthritic patients, daily oral doses of about 600 milligrams of boswellic acid for eight weeks reduced symptoms and improved clinical parameters.72 of about 1.1 grams Boswellia resin for six weeks reduced signs and symptoms in patients with ulcerative colitis (82 percent went into remission), while daily oral doses of about 900 milligrams for six weeks reduced symptoms in patients with bronchial asthma (70 percent showed improvement).73,74

Oral doses per day of

Boswellic acid has induced differentiation and/or decreased proliferation of leukemia or central nervous system cancer cells in vitro. The effective concentrations ranged from 2 to 40 |M:

• Boswellic acid inhibited proliferation of four human brain cancer cell lines at an IC50 of 30 to 40 mM.55

• Boswellic acid inhibited proliferation of 11 lines of meningiomas obtained from patients at an IC50 of 2 to 8 mM.60

• Boswellic acid induced differentiation in human leukemia cells at 11 to 22 |M.63,75

• Boswellic acid induced apoptosis in human leukemia cells at an IC50 of 30 |M.58

• Boswellic acid inhibited proliferation of human leukemia cells by 72 percent at 4 |M.54

• Boswellic acid acetate at concentrations of less than 24 mM induced differentiation in three of five leukemia cell lines; the proliferation of all five cell lines was inhibited at concentrations of about 40 mM or

Oral doses per day of

TABLE 21.5 POTENTIAL ANTICANCER ACTIONS OF BOSWELLIC ACID

ACTIVITY

KNOWN EFFECTS

AS AN EICOSANOID INHIBITOR, MAY:

AS A HYALURONIDASE INHIBITOR, MAY:

Chapter 2: Mutations, Gene Expression, and Proliferation

Inhibit topoisomerases

x

Chapter 3: Results of Therapy at the Cellular Level

Induce differentiation

x

Induce apoptosis

x

x

Chapter 5: Transcription Factors and Redox Signaling

Inhibit NF-kB activity

x

Chapter 6: Cell-to-Cell Communication

Affect CAMs

x

Chapters 7 and 8: Angiogenesis

Inhibit angiogenesis

x

x

Inhibit bFGF effects

x

Inhibit eicosanoid effects

x

Inhibit VEGF effects

x

Chapters 9 and 10: Invasion and Metastasis

Inhibit invasion

x

Inhibit hyaluronidase, beta-glucuronidase, or elastase

x

x

Inhibit collagenase effects

x

Inhibit GAG synthesis

x

Inhibit cell migration

x

x

Inhibit metastasis

x

In addition to the above, at least one in-vitro study has reported that boswellic acid interacts synergistically with other natural compounds. In that study, boswellic acid was a weak inducer of differentiation in human leukemia cells, but its action greatly increased in the presence of daidzein.56 The potential anticancer actions of boswellic acid are listed in Table 21.5.

less.

Three animal studies reported that boswellic acid produced antitumor effects. In the first, oral doses of 75, 150, and 300 mg/kg per day reduced the growth of transplanted brain cancer cells in rats.62 The human equivalent of 150 mg/kg per day in rats is 2.4 grams per day. In the second study, intraperitoneal administration of 25 to 50 mg/kg inhibited growth and induced the differentiation of transplanted leukemia cells in mice.63,75 The equivalent human oral dose is about 340 to 680 milligrams per day. In the third, oral administration of 720 mg/kg of Boswellia extract increased the survival of rats injected with brain cancer cells.64 This extract contained 20 percent boswellic acid.76 The dose of boswellic acid was then about 144 mg/kg, or about 2.3 grams as scaled to humans.

TABLE 21.6 ESTIMATED THERAPEUTIC AND LOAEL DOSES FOR BOSWELLIC ACID*

DESCRIPTION

DOSE (g/day)

Required dose as scaled from animal antitumor studies

0.34 to 2.4

Required dose as scaled from animal antiinflammatory studies

0.73 to 3.2

Doses used in human anticancer studies

3.6 to 5.4 as Boswellia extract^

Required cytotoxic dose as determined from pharmacokinetic calculations

2.3

Target dose based on an average from animal antitumor studies and pharmacokinetic calculations

1.8

Minimum required antitumor dose assuming 15fold synergistic benefits

0.12

Commonly studied human dose in noncancerous conditions

0.6 (boswellic acid) 0.9 to 1.1 (Boswellia extract)

Estimated LOAEL dose

2.7

Tentative dose recommendation for further research

1.8

Minimum degree of synergism required

none

See Appendix J for details. ^ The concentration of boswellic acid in the Boswellia extracts used is uncertain.

At least two human studies have also been conducted. In the first, oral administration of about 3.6 grams daily of Boswellia extract tablets reduced brain edema in brain tumor patients.65 This effect could be attributed largely to its anti-inflammatory action. In another study, on 19 children with brain cancer, a boswellic acid product given orally at a daily average dose of 77 mg/kg for nine months produced palliative benefits, including relief of general symptoms and transient or sometimes longer-lasting regression of neurological symptoms.66 The equivalent adult dosage would be about 5.4 grams. Because the concentration of boswellic acid in the products used in the human studies is uncertain, the doses of boswellic acid used are also uncertain.

3.6-gram per day dose of Boswellia extract used in the human study on brain tumor patients; the actual boswellic acid content in the extract was not given.

The commonly prescribed dose of Boswellia resin for noncancerous conditions in Chinese herbal medicine is 3 to 9 grams per day, although the actual content of boswellic acid in the resin has not been reported. Human anti-inflammatory studies have used doses of 600 milligrams per day of boswellic acid and 0.9 to 1.1 grams of resin per day. The LOAEL dose for boswellic acid is estimated at 2.7 grams daily (see Appendix J).

Dose calculations for boswellic acid are summarized in Table 21.6, with the tentative recommended dose listed as 1.8 grams per day. This value is equal to the target human dose. Boswellia extract is the most common source of boswellic acid, and dose estimates for it will differ, depending on its boswellic acid content.

Because the target dose is achievable, synergistic interactions may not be required for boswellic acid to produce an anticancer effect in humans. Still, it may greatly benefit from synergistic interactions and is best tested in combinations.

The dose of 1.8 grams recommended in Table 21.6 might produce analgesic or sedative effects, which could be useful in some situations. Such effects occurred at an intraperitoneal dose of 55 mg/kg in rats but were slight at 20 mg/kg.77 The equivalent human oral dose of a 55-mg/kg dose in rats is about 1.2 grams.

Estimated Therapeutic and LOAEL Doses of Boswellic Acid

The required dose scaled from animal studies is similar to the one calculated from pharmacokinetic and in-vitro data. The former is 340 milligrams to 2.4 grams per day, and doses scaled from anti-inflammatory experiments are similar. Using a target in-vivo concentration of 15 mM, the required boswellic acid dose from phar-macokinetic calculations is about 2.3 grams per day. We use an average of 0.34, 2.4, 2.3, and 2.3 grams, or 1.8 grams per day as our target human dose, which is nearly the same target dose estimated for asiatic acid. This dose also seems reasonable in comparison to the

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