Even though the degradation of ginsenosides has been thoroughly studied in animals and in vitro using acids, enzymes, and intestinal bacteria, knowledge concerning the systemic availability of ginsenosides and their degradation products in humans is generally lacking. Therefore, the attention in this article is focused on the identification of ginsenosides and their hydrolysis products reaching the systemic circulation in man. This is of great importance in understanding clinical effects, preventing herb-drug interactions, and optimizing the biopharmaceutical properties of ginseng preparations. Using a sensitive mass spectrometric method, which is specific for the identification of ginsenosides in complex biological matrices, the degradation pathway of ginsenosides in the gastrointestinal tract of humans could be elucidated following the oral administration of ginseng. Within the frame of a pilot study, human plasma and urine samples of two subjects were screened for ginsenosides and their possible degradation products. In general, the urine data coincided well with the plasma data. In both volunteers the same hydrolysis products, which are not originally present in the Ginsana extract (Pharmaton S.A., Lugano, Switzerland) ingested, were identified in plasma and urine. It was shown that two hydrolysis products of the protopanaxatriol ginsenosides, namely G-Rh₁ and G-F₁ may reach the systemic circulation. In addition, compound-K, the main intestinal bacterial metabolite of the protopanaxadiol ginsenosides, was detected in plasma and urine. These products are probably responsible for the action of ginseng in humans. In opposition to previous reports, G-Rb₁ was identified in plasma and urine of one subject.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand activated transcription factor, belonging to the metazoan family of nuclear hormone receptors. Activation of PPARγ increases the transcription of enzymes involved in primary metabolism, leading to lower blood levels of fatty acids and glucose. Hence, PPARγ represents the major target for the glitazone type of drugs currently being used clinically for the treatment of type 2 diabetes. Furthermore, activators of PPARγ show beneficial anti-inflammatory and anti-tumour effects. Utilizing a fusion receptor of the yeast Gal4-DNA binding domain joined to the hinge region and ligand binding domain of the human PPARγ in combination with a Gal4-driven luciferase reporter gene, cotransfected into Cos7 cells, we tested sage and rosemary extracts prepared with 80 % aqueous ethanol for possible PPARγ activation. This revealed that both extracts are capable of selectively activating Gal4-PPARγ fusion receptor, in a concentration-dependent manner, with EC₅₀ values of 22.8 ± 8.4 mg/L and 33.7 ± 7.3 mg/L for rosemary and sage, respectively. Subsequent analysis of the characteristic constituents revealed the phenolic diterpene compounds carnosol, present in both herbs, and carnosic acid to be active principles of these extracts, showing EC₅₀ values of 41.2 ± 5.9 μM and 19.6 ± 2.0 μM, respectively. Thus it can be concluded that the glucose lowering effect reported recently for rosemary may be attributed to PPARγ activation. Moreover, our observations may also explain the anti-inflammatory and antiproliferative effects of both compounds published previously.

BACKGROUND: Patients irradiated for brain tumors often suffer from cerebral edema and are usually treated with dexamethasone, which has various side effects. To investigate the activity of Boswellia serrata (BS) in radiotherapy‐related edema, we conducted a prospective, randomized, placebo‐controlled, double‐blind, pilot trial.METHODS: Forty‐four patients with primary or secondary malignant cerebral tumors were randomly assigned to radiotherapy plus either BS 4200 mg/day or placebo. The volume of cerebral edema in the T2‐weighted magnetic resonance imaging (MRI) sequence was analyzed as a primary endpoint. Secondary endpoints were toxicity, cognitive function, quality of life, and the need for antiedematous (dexamethasone) medication. Blood samples were taken to analyze the serum concentration of boswellic acids (AKBA and KBA).RESULTS: Compared with baseline and if measured immediately after the end of radiotherapy and BS/placebo treatment, a reduction of cerebral edema of >75% was found in 60% of patients receiving BS and in 26% of patients receiving placebo (P = .023). These findings may be based on an additional antitumor effect. There were no severe adverse events in either group. In the BS group, 6 patients reported minor gastrointestinal discomfort. BS did not have a significant impact on quality of life or cognitive function. The dexamethasone dose during radiotherapy in both groups was not statistically different. Boswellic acids could be detected in patients' serum.CONCLUSIONS: BS significantly reduced cerebral edema measured by MRI in the study population. BS could potentially be steroid‐sparing for patients receiving brain irradiation. Our findings will need to be further validated in larger studies. Cancer 2011. © 2011 American Cancer Society.

The anti-inflammatory potential of Boswellia serrata gum resin extracts has been demonstrated in vitro and in animal studies as well as in pilot clinical trials. However, pharmacokinetic studies have evidenced low systemic absorption of boswellic acids (BAs), especially of KBA and AKBA, in rodents and humans. This observation has provided a rationale to improve the formulation of Boswellia extract. We present here the results of a murine comparative bioavailability study of Casperome™, a soy lecithin formulation of standardized B. serrata gum resin extract (BE), and its corresponding non-formulated extract. The concentration of the six major BAs [11-keto-β-boswellic acid (KBA), acetyl-11-keto-β-boswellic acid (AKBA), β-boswellic acid (βBA), acetyl-β-boswellic acid (AβBA), α-boswellic acid (αBA), and acetyl-α-boswellic acid (AαBA)] was evaluated in the plasma and in a series of tissues (brain, muscle, eye, liver and kidney), providing the first data on tissue distribution of BAs. Weight equivalent and equimolar oral administration of Casperome™ provided significantly higher plasma levels (up to 7-fold for KBA, and 3-fold for βBA quantified as area under the plasma concentration time curve, AUC(last)) compared to the non-formulated extract. This was accompanied by remarkably higher tissue levels. Of particular relevance was the marked increase in brain concentration of KBA and AKBA (35-fold) as well as βBA (3-fold) following Casperome™ administration. Notably, up to 17 times higher BA levels were observed in poorly vascularized organs such as the eye. The increased systemic availability of BAs and the improved tissue distribution, qualify Casperome™ for further clinical development to fully exploit the clinical potential of BE.

Boswellia serrata resin dry extract is among the few herbal remedies designated with an orphan drug status for the treatment of peritumoral brain edema. In addition, boswellic acids (BAs), the main active ingredients of B. serrata extracts, have potent anti-inflammatory properties, and may represent promising agents for the treatment of inflammatory diseases. Pharmacokinetic studies, however, revealed poor bioavailability, especially of 11-keto-β-boswellic acid (KBA) and 3-acetyl-11-keto-β-boswellic acid (AKBA), the most potent BAs. To address the question of whether BAs are extensively metabolized, we determined the metabolic stability of KBA and AKBA in vitro, investigated the in vitro metabolism of BAs, and compared the metabolic profiles of KBA and AKBA with those obtained in rats in vivo. In rat liver microsomes and hepatocytes as well as in human liver microsomes, we found that KBA but not AKBA undergoes extensive phase I metabolism. Oxidation to hydroxylated metabolites is the principal metabolic route. In vitro, KBA yielded metabolic profiles similar to those obtained in vivo in rat plasma and liver, whereas no metabolites of AKBA could be identified in vivo. Furthermore, AKBA is not deacetylated to KBA. This study indicates that the efficacy of B. serrata extract may be enhanced by increasing the bioavailability of AKBA.