Isomitraphylline

Biotechnol Lett. 2015 Dec;37(12):2489-96.

Long-term response on growth, antioxidant enzymes, and secondary metabolites in salicylic acid pre-treated Uncaria tomentosa microplants.[Pubmed: 26272395]

To obtain micro propagated Uncaria tomentosa plantlets with enhanced secondary metabolites production, long-term responses to salicylic acid (SA) pre-treatments at 1 and 100 μM were evaluated after propagation of the plantlets in a SA-free medium.
METHODS AND RESULTS:
SA pre-treatments of single node cuttings OF U. tomentosa produced long-term responses in microplants grown for 75 days in a SA-free medium. Reduction in survival rate, root formation, and stem elongation were observed only with 100 μM SA pre-treatments with respect to the control (0 + DMSO).Both pre-treatments enhanced H2O2 and inhibited superoxide dismutase and catalase activities, while guaiacol peroxidase was increased only with 1 μM SA. Also, both pre-treatments increased total monoterpenoid oxindole alkaloids by ca. 55 % (16.5 mg g(-1) DW), including isopteropodine, speciophylline, mitraphylline, Isomitraphylline, rhynchopylline, and isorhynchopylline; and flavonoids by ca. 21 % (914 μg g(-1) DW), whereas phenolic compounds were increased 80 % (599 μg g(-1) DW) at 1 μM and 8.2 % (359 μg g(-1) DW) at 100 μM SA.
CONCLUSIONS:
Pre-treatment with 1 μM SA of U.tomentosa microplants preserved the survival rate and increased oxindole alkaloids, flavonoids, and phenolic compounds in correlation with H2O2 and peroxidase activity enhancements, offering biotechnological advantages over non-treated microplants.

Pharmacol Rep. 2007 Sep-Oct;59(5):565-72.

Antiproliferative activity of various Uncaria tomentosa preparations on HL-60 promyelocytic leukemia cells.[Pubmed: 18048957]

The woody Amazonian vine Uncaria tomentosa (cat's claw) has been recently more and more popular all over the world as an immunomodulatory, antiinflammatory and anti-cancer remedy.
METHODS AND RESULTS:
This study investigates anti-proliferative potency of several cat's claw preparations with different quantitative and qualitative alkaloid contents on HL-60 acute promyelocytic human cells by applying trypan blue exclusion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay (MTT).
CONCLUSIONS:
By standardization and statistical comparison of the obtained results pteropodine and Isomitraphylline are indicated to be most suitable for standardization of medical cat's claw preparations.

Br J Haematol. 2006 Mar;132(5):615-22.

Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells.[Pubmed: 16445836]

Natural products are still an untapped source of promising lead compounds for the generation of antineoplastic drugs.
METHODS AND RESULTS:
Here, we investigated for the first time the antiproliferative and apoptotic effects of highly purified oxindole alkaloids, namely isopteropodine (A1), pteropodine (A2), Isomitraphylline (A3), uncarine F (A4) and mitraphylline (A5) obtained from Uncaria tomentosa, a South American Rubiaceae, on human lymphoblastic leukaemia T cells (CCRF-CEM-C7H2). Four of the five tested alkaloids inhibited proliferation of acute lymphoblastic leukaemia cells. Furthermore, the antiproliferative effect of the most potent alkaloids pteropodine (A2) and uncarine F (A4) correlated with induction of apoptosis. After 48 h, 100 micromol/l A2 or A4 increased apoptotic cells by 57%. CEM-C7H2 sublines with tetracycline-regulated expression of bcl-2, p16ink4A or constitutively expressing the cowpox virus protein crm-A were used for further studies of the apoptosis-inducing properties of these alkaloids. Neither overexpression of bcl-2 or crm-A nor cell-cycle arrest in G0/G1 phase by tetracycline-regulated expression of p16INK4A could prevent alkaloid-induced apoptosis.
CONCLUSIONS:
Our results show the strong apoptotic effects of pteropodine and uncarine F on acute leukaemic lymphoblasts and recommend the alkaloids for further studies in xenograft models.

Nat Prod Commun. 2009 Jul;4(7):907-10.

Phytochemical characterization of the leaves of Mitragyna speciosa grown in U.S.A.[Pubmed: 19731590]

Mitragyna speciosa (Rubiaceae) has traditionally been used in the tropical regions of Asia, Africa and Indonesia as a substitute for opium. Indole alkaloids are the most common compounds that have been isolated.
METHODS AND RESULTS:
We investigated the constituents of the leaves of M. speciosa that was grown at the University of Mississippi. Several alkaloids were isolated, including ajmalicine, corynantheidine, Isomitraphylline, mitraphylline, paynantheine, isocorynantheidine, 7-hydroxymitragynine and mitragynine, but their percentages were lower than those in a commercial Thai sample of "kratom". In addition, we isolated the flavonoid epicatechin, a saponin daucosterol, the triterpenoid saponins quinovic acid 3-O-beta-D-quinovopyranoside, quinovic acid 3-O-beta-D-glucopyranoside, as well as several glycoside derivatives including 1-O-feruloyl-beta-D-glucopyranoside, benzyl-beta-D-glucopyranoside, 3-oxo-alpha-ionyl-O-beta-D-glucopyranoside, roseoside, vogeloside, and epivogeloside.
CONCLUSIONS:
This is the first report of the last group of compounds having been isolated from a Mitragyna species. Biological studies are currently underway to test these compounds for opioid activity.