Natural products in Helicobacter pylori research

(in-vitro data)

In most developing countries, plant-based medicines are commonly used to treat gastrointestinal ailments, including gastritis, peptic ulcer disease and diarrhea. Thus, considering the strong association between these conditions and Helicobacter pylori infections, it should not be surprising that some plant-based medicines would have activity against Helicobacter pylori in vitro.

The first investigation of the in-vitro efficacy of plant extracts against Helicobacter pylori was published in 1991. This group reported that extracts of 13 Malagasy medicinal plants were effective against a number of clinical strains of Helicobacter pylori in vitro. In 1996, Fabry and coworkers reported that a number of east African medicinal plant extracts had inhibitory effects on the growth of Helicobacter pylori in vitro. One plant, Terminalia spinosa was reported to be the most active, with a minimum inhibitory concentration (MIC) range of 62.5-500 µg/mL. Extracts of Tbymus vulgaris (aqueous extract) and Cinnamonum zeylanicum (alcohol extract) were also reported to inhibit the growth of the bacterium at concentrations of 3.5 mg/mL.

In 1997, investigators discovered that common food plants such as garlic, soybean and fresh vegetables may be protective against Helicobacter pylori infections. An aqueous extract of garlic (Allium sativum) inhibited the growth of Helicobacter pylori strains at concentrations of 40 µg/mL and MICs of 8-32 µg/mL for garlic oil against several Helicobacter pylori strains were reported.

Rabdosia tricbocarpa, a traditional remedy for gastric and stomachic complaints in Japan, also inhibits the growth of Helicobacter pylori in vitro, because of a diterpene trichorabdal A. In 1999, the anti-Helicobacter pylori effects of seven Turkish plant extracts, used in folk medicine for the treatment of gastric ailments including peptic ulcers, were reported. Extracts of the flowers of Cistus laurifolius, cones of Cedrus libani, aerial parts of Centaurea solstitialis ssp. solstitialis, fruits of Momordica charantia, aerial parts of Sambucus ebulus, and flowering herbs of Hypericum perforatum were active with a minimum inhibitory concentration range of between 1.95 and 250 µg/mL. In 2003, a screening of 20 plant extracts from Thailand used to treat gastrointestinal ailments reported that over 50% of the plant species tested had anti-Helicobacter pylori activity. Methanol extracts of Myristica fragrans (aril) inhibited the growth of all Helicobacter pylori strains with a MIC of 12.5 µg/mL; extracts from Barringtonia acutangula (leaf) and Kaempferia galanga (rhizome) had a minimum inhibitory concentration of 25 µg/mL; Cassia grandis (leaf), Cleome viscosa (leaf), Myristica fragrans (leaf) and Syzygium aromaticum (leaf) had MICs of 50 Lig/mL. Extracts with a minimum inhibitory concentration of 100 µg/mL included Pouzolzia pentandra (leaf), Cycas siamensis (leaf), Litsea elliptica (leaf) and Melaleuca quinquenervia (leaf).

Ginger root (Zingiber officinale), a plant well known worldwide to treat gastrointestinal ailments, also has activity against Helicobacter pylori. Methanol extracts of ginger rhizome inhibited the growth of 19 Helicobacter pylori strains in vitro with a MIC range of 6.25-50 µg/mL. The 6-, 8- and 10-gingerols all had varying degrees of activity, with a minimum inhibitory concentration range of 0.78 to 12.5 µg/mL and interestingly had significant activity against the CagA cancer-causing strains. Curcumin, a polyphenolic constituent isolated from turmeric (Curcuma longa), and a methanol extract of the dried, powdered turmeric rhizome were both active against 19 strains of Helicobacter pylori, including five CagA strains. The MIC range was 6.25-50 Lig/mL. In addition, red wine extract (Vitis vinifera) and resveratrol inhibited the growth of Helicobacter pylori in vitro. Resveratrol, a stilbene present in red wine had a minimum inhibitory concentration of 25 µg/mL, while the red wine extract had a MIC range of 25-50 µg/mL. Interestingly, resveratrol was more active against CagA strains of Helicobacter pylori than CagAstrains.

Two indigenous American plants, Sanguinaria canadensis and Hydrastis canadensis, used traditionally by the Native American Indians for the treatment of gastrointestinal ailments, have also been shown to be active against Helicobacter pylori. Methanol extracts of the rhizome or suspension cell cultures of S. canadensis had a minimum inhibitory concentration range of 12.5-50.0 µg/mL. Three isoquinoline alkaloids were identified in the active fraction. Sanguinarine and chelerythrine, two benzophenanthridine alkaloids, inhibited the growth of the Helicobacter pylori, with a MIC of 50 and 100 µg/mL, respectively. Protopine, an alkaloid, also inhibited the growth of bacterium, with a MIC of 100 µg/mL. A crude methanol extract of H. canadensis rhizomes was very active, with a minimum inhibitory concentration of 12.5 µg/mL (range 0.78 to 25 µg/mL). Two isoquinoline alkaloids, berberine and β-hydrastine, were identified as the active constituents, and having a MIC of 12.5 and 100.0 µg/mL, respectively.

The in-vitro susceptibility of 15 Helicobacter pylori strains to natural products that had a history of traditional use in the treatment of GI disorders was recently assessed. Methanol extracts of Myristica fragrans (seed) had a minimum inhibitory concentration of 12.5 µg/mL and Rosmarinus officinalis (rosemary leaf) had a MIC of 25 µg/mL. Methanol extracts of botanicals with a minimum inhibitory concentration of 50 µg/mL included Achillea millefolium (aerial parts), Foeniculum vulgare (seed), Passiflora incarnata (aerial parts), Origanum majorana (herb) and a (1:1) combination of Curcuma longa (root) and ginger rhizome. Botanical extracts with a MIC of 100 µg/mL included Carum carvi (seed), Elettaria cardamomum (seed), Gentiana lutea (roots), Juniper communis (berry), Lavandula angustifolia (flowers), Melissa officinalis (leaves), Mentba piperita (leaves) and Pimpinella anisum (seed). Methanol extracts of Matricaria recutita (flowers) and Ginkgo biloba (leaves) had a minimum inhibitory concentration of 100 Lig/mL. A traditional medicine from Iceland, the lichen Cetaria islandica, also used to treat gastrointestinal ailments has anti-Helicobacter pylori activity. Protolichesterinic acid, an aliphatic α-methylene-γ-lactone, was identified as one of the active constituents. The MIC range of protolichesterinic acid, in free as well as salt form, was 16-64 Lig/mL.

The antibacterial activity of Gosyuyu, a crude extract from the fruit of Evodia rutaecarpa, a Chinese herbal medicine, has also been tested for activity against Helicobacter pylori in vitro. Two compounds were identified as the active constituents and were the quinolone alkaloids, 1-methyl-2-[(Z)-8-tridecenyl]-4-(1H)-quinolone and 1-methyl-2-[(Z)-7-tridecenyl]-4-(1H)-quinolone. The minimum inhibitory concentration of these compounds against reference strains and clinically isolated Helicobacter pylori strains was <0.05 µg/mL, similar to that of amoxicillin and clarithromycin. Finally, in a recent report, screening of 70 medicinal plants from Greece, led to the discovery of a number of plants with anti-Helicobacter pylori activity. Extracts of Anthemis melanolepis, Cerastium candidissimum, Chamomilla recutita, Conyza albida, Dittricbia viscosa, Origanum vulgare and Stacbys alopecuros were active against one standard strain and 15 clinical isolates of Helicobacter pylori.

In addition to antibacterial activity, tea (Camellia sinensis) and rosemary (Rosmarinus officinalis L.) extracts inhibit Helicobacter pylori urease in vitro. Green tea extract showed the strongest inhibition of Helicobacter pylori urease, with a minimum inhibitory concentration of 13 µg/mL. Active principles were identified as catechins, with the hydroxyl group of 5′ position appearing important for urease inhibition.