Extract of Artemisia dracunculus L. Modulates Osteoblast Proliferation and Mineralization.

Thiazolidinediones (TZD) significantly improve insulin sensitivity via action on adipocytes. Unfortunately, TZDs also degrade bone by inhibiting osteoblasts. An extract of Artemisia dracunculus L., termed PMI5011, improves blood glucose and insulin sensitivity via skeletal muscle, rather than fat, and may therefore spare bone. Here, we examine the effects of PMI5011 and an identified active compound within PMI5011 (2',4'-dihydroxy-4-methoxydihydrochalcone, DMC-2) on pre-osteoblasts. We hypothesized that PMI5011 and DMC-2 will not inhibit osteogenesis. To test our hypothesis, MC3T3-E1 cells were induced in osteogenic media with and without PMI5011 or DMC-2. Cell lysates were probed for osteogenic gene expression and protein content and were stained for osteogenic endpoints. Neither compound had an effect on early stain outcomes for alkaline phosphatase or collagen. Contrary to our hypothesis, PMI5011 at 30 µg/mL significantly increases osteogenic gene expression as early as day 1. Further, osteogenic proteins and cell culture mineralization trend higher for PMI5011-treated wells. Treatment with DMC-2 at 1 µg/mL similarly increased osteogenic gene expression and significantly increased mineralization, although protein content did not trend higher. Our data suggest that PMI5011 and DMC-2 have the potential to promote bone health via improved osteoblast maturation and activity.

Artemisia supplementation differentially affects the mucosal and luminal ileal microbiota of diet-induced obese mice.

OBJECTIVE: The gut microbiome has been implicated in obesity and metabolic syndrome; however, most studies have focused on fecal or colonic samples. Several species of Artemisia have been reported to ameliorate insulin signaling both in vitro and in vivo. The aim of this study was to characterize the mucosal and luminal bacterial populations in the terminal ileum with or without supplementation with Artemisia extracts. METHODS: Following 4 wk of supplementation with different Artemisia extracts (PMI 5011, Santa or Scopa), diet-induced obese mice were sacrificed and luminal and mucosal samples of terminal ileum were used to evaluate microbial community composition by pyrosequencing of 16 S rDNA hypervariable regions. RESULTS: Significant differences in community structure and membership were observed between luminal and mucosal samples, irrespective of diet group. All Artemisia extracts increased the Bacteroidetes to Firmicutes ratio in mucosal samples. This effect was not observed in the luminal compartment. There was high interindividual variability in the phylogenetic assessments of the ileal microbiota, limiting the statistical power of this pilot investigation. CONCLUSIONS: Marked differences in bacterial communities exist depending on the biogeographic compartment in the terminal ileum. Future studies testing the effects of Artemisia or other botanical supplements require larger sample sizes for adequate statistical power.

Artemisia dracunculus L. polyphenols complexed to soy protein show enhanced bioavailability and hypoglycemic activity in C57BL/6 mice.

OBJECTIVE: Scientifically validated food-based interventions are a practical means of addressing the epidemic of metabolic syndrome. An ethanolic extract of Artemisia dracunculus L. (PMI-5011) containing bioactive polyphenols, such as 2', 4'-dihydroxy-4-methoxydihydrochalcone (DMC-2), improved insulin resistance in vitro and in vivo. Plant polyphenols are concentrated and stabilized when complexed to protein-rich matrices, such as soy protein isolate (SPI), which act as effective food-based delivery vehicles. The aim of this study was to compare the bioaccessibility, bioavailability, and efficacy of polyphenols extracted from A. dracunculus and delivered as PMI-5011 (ethanolic extract alone), formulated with the non-food excipient Gelucire(®), (5011- Gelucire), or sorbed to SPI (5011-Nutrasorb(®)). METHODS: PMI-5011, 5011-Gelucire or 5011-Nutrasorb each containing 162 µg of DMC-2 was delivered to the TNO intestinal model-1 of the human upper gastrointestinal tract to compare the effect of delivery vehicle on DMC-2 bioaccessibility. C57BL6/J mice were orally administered 5011-Nutrasorb or PMI-5011 to compare effects of polyphenol-protein complexation on acute hypoglycemic activity and bioavailability of DMC-2 in serum. RESULTS: At 500 mg/kg, 5011-Nutrasorb and PMI-5011 had similar hypoglycemic activity in a high-fat diet-induced diabetes mouse model despite the fact that 5011-Nutrasorb delivered 15 times less DMC-2 (40 versus 600 µg/kg). This can be partially explained by eight times greater DMC-2 absorption into serum from 5011-Nutrasorb than from PMI-5011. TNO intestinal model-1 experiments confirmed higher total bioaccessibility of DMC-2 in vitro when delivered in 5011-Nutrasorb (50.2%) or Gelucire-5011 (44.4%) compared with PMI-5011 (27.1%; P = 0.08). CONCLUSION: Complexation with soy protein makes antidiabetic A. dracunculus polyphenols more bioavailable and bioaccessible.

Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture.

AIMS: Bioactives of Artemisia dracunculus L. (termed PMI 5011) have been shown to improve insulin action by increasing insulin signalling in skeletal muscle. However, it was not known if PMI 5011's effects are retained during an inflammatory condition. We examined the attenuation of insulin action and whether PMI 5011 enhances insulin signalling in the inflammatory environment with elevated cytokines. METHODS: Muscle cell cultures derived from lean, overweight and diabetic-obese subjects were used. Expression of pro-inflammatory genes and inflammatory response of human myotubes were evaluated by real-time polymerase chain reaction (RT-PCR). Insulin signalling and activation of inflammatory pathways in human myotubes were evaluated by multiplex protein assays. RESULTS: We found increased gene expression of monocyte chemoattractant protein 1 (MCP1) and TNFα (tumour necrosis factor alpha), and basal activity of the NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway in myotubes derived from diabetic-obese subjects as compared with myotubes derived from normal-lean subjects. In line with this, basal Akt phosphorylation (Ser473) was significantly higher, while insulin-stimulated phosphorylation of Akt (Ser473) was lower in myotubes from normal-overweight and diabetic-obese subjects compared with normal-lean subjects. PMI 5011 treatment reduced basal phosphorylation of Akt and enhanced insulin-stimulated phosphorylation of Akt in the presence of cytokines in human myotubes. PMI 5011 treatment led to an inhibition of cytokine-induced activation of inflammatory signalling pathways such as Erk1/2 and IkBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha)-NFkB and moreover, NFkB target gene expression, possibly by preventing further propagation of the inflammatory response within muscle tissue. CONCLUSIONS: PMI 5011 improved insulin sensitivity in diabetic-obese myotubes to the level of normal-lean myotubes despite the presence of pro-inflammatory cytokines.