Ukrain

Greater celandine/Drug Interactions:

  • AnalgesicsAnalgesics: In a prospective multicenter pilot study, Cholagogum F Nattermann? (dried extracts of Scholkraut and Curcuma) reduced right upper quadrant colicky pain more effectively than placebo in 76 patients with biliary dyskinesia (1).
  • AntibioticsAntibiotics: In a systematic review evaluating in vivo, in vitro, and animal research, Chelidonium majus has been reported to be one of the most active antimicrobial plants with antibacterial activity against S. aureus, Bacillus cereus, multiresistant Enterococci (47). In animal research, UkrainT administered subcutaneously to balb/C mice had effects on E. coli and S. aureus (78; 79). Researchers also report that lectins from Chelidonium majus L. (CML) have demonstrated potent antimicrobial properties against multiresistant Enterococci and Staphylococci (80).
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): The major alkaloids from plants such as greater celandine and drugs such as "UkrainT" (thiophosphoric acid derivative of a sum of the alkaloids isolated from greater celandine) have been shown to be irreversible inhibitors of the oxidative deamination reaction of serotonin and tyramine catalyzed by rat liver mitochondrial monoamine oxidase (MAO) (8). Chelironine and the drug UkrainT were the strongest inhibitors of the reaction among the agents studied.
  • Antidepressants, selective serotonin reuptake inhibitors (SSRIs)Antidepressants, selective serotonin reuptake inhibitors (SSRIs): Research with intraperitoneal administration of UkrainT in rats has shown that one of the primary actions of UkrainT involves inhibition of the serotonergic system (7).
  • Antidiabetic agentsAntidiabetic agents: Greater celandine has traditionally been used for the treatment of diabetes; however, administration of dried leaves of celandine (6.25% of diet by weight) to streptozotocin induced diabetic rats lacked an effect on the development of hyperphagia polydipsia, body weight loss, hyperglycemia, and hypoinsulinemia (20).
  • Antifungal agentsAntifungal agents: In a systematic review evaluating in vivo, in vitro, and animal research, Chelidonium majus has been reported to be one of the most active antimicrobial plants with antifungal activity against Candida albicans, Fusarium oxysporum, and Botrytis cinerea (47). Aqueous extracts of Chelidonium majus L. demonstrated considerable inhibitory action against 10 Fusarium strains. However, methanolic extracts showed the best results. Root extracts showed more powerful growth inhibition than shoot extracts. Since most Fusarium strains have high resistance to conventional fungicides, the authors proposed Chelidonium majus as a good source of constituents valuable for the treatment of Fusarium fungal infections (81).
  • Anti-inflammatoriesAnti-inflammatories: In a systematic review evaluating animal research in mice, Chelidonium majus extract suppressed arthritis by decreasing production of TNF-alpha, interleukin-6, interferon-gamma, B cells, and gamma delta T cells (47). According to a laboratory study, stylopine, a major constituent of Chelidonium majus L. leaf, suppresses nitrous oxide (NO) and prostaglandin E2 (PGE2) production in macrophages by inhibiting the iNOS and COX-2 expressions (24). These biological activities of stylopine may contribute to the anti-inflammatory activity of Chelidonium majus. It has also been proposed that quaternary benzophenanthridine alkaloids from Chelidonium majus may play a role in the anti-inflammatory activity (10).
  • AntineoplasticsAntineoplastics: In patients with advanced esophageal cancer, the combination of Chelidonium majus L. and endoxan appeared to mask the immunological response of the host without instigating the degeneration of cancer tissue seen in patients who took Chelidoniummajus alone (54). In in vitro research, UkrainT induced apoptosis in a panel of cancer cell lines (including HeLa cervical cancer cells) through activation of the intrinsic cell death pathway (82). Systematic reviews have reported that UkrainTM (alkaloids from Chelidonium majus conjugated with thiophosphoric acid) may have less adverse effects and some benefit in breast, bladder, rectal and colorectal, pancreatic cancers, and Kaposi sarcoma vs. conventional anticancer medications (47) and that use of UkrainT to treat cancer is supported by many clinical and pre-clinical trials in a range of malignancies; however, many of the studies had methodological limitations (57).
  • AntiretroviralsAntiretrovirals: A substance isolated from the freshly prepared crude extract of Chelidonium majus L. has been shown to have antiretroviral activity against HIV-1 in vitro (83).
  • Antispasmodic agentsAntispasmodic agents: Chelidonium majus extract demonstrated weak antispasmodic activity against acetylcholine (ACh)-induced contraction on isolated rat ileal smooth muscle (16). In another study, two ethanolic dry extracts from Chelidonium majus L. (one with a defined content of the main alkaloids (chelidonine, protopine, and coptisine) and one with the alkaloids themselves) demonstrated antispasmodic effects on isolated ileum of guinea-pigs (84). Chelidonine and protopine exhibited the known papaverine-like musculotropic action, whereas coptisine (up to 3.0 x 10-5g/mL) was ineffective in the BaCl2-stimulated ileum. All three alkaloids antagonized carbachol and electric field stimulated contractions.
  • Antiulcer agentsAntiulcer agents: Based on animal study, Chelidonium majus extract alone and in a combination with extracts from the plants Iberis amara, Melissa officinalis, Matricaria recutita, Carum carvi, Mentha x piperita, Glycyrrhiza glabra, Angelica archangelica, and Silybum marianum (STW 5 - Iberogast?) produced a dose dependent anti-ulcerogenic activity against indometacin induced gastric ulcers in rats (28).
  • AntiviralsAntivirals: A substance isolated from the freshly prepared crude extract of Chelidonium majus L. has been shown to have antiretroviral activity against HIV-1 in vitro (83). Various components of UkrainT have reported inhibitory effects on grippe virus of A type (England) 42/72 (H3N2) in Swiss albino mice, and these substances include the totality of Chelidonium majus alkaloids, thiophosphamide (the alkalizing agent), the sum of alkaloids modified by thiotepa, and some other alkaloids as their alkalized derivatives (85).
  • BisphosphonatesBisphosphonates: UkrainT may have antiosteoporotic effects because of its "anabolic effect" on bone in ovariectomized rats. The proposed mechanism of action in this regard is a stimulating effect on gonadal hormone production, especially estrogen. However, the data on UkrainT's effects on bone metabolism is conflicting (3; 4; 5; 6).
  • Choleretic agentsCholeretic agents: The total ethanolic extract of Chelidonium majus L. were tested for their choleretic activity using the isolated perfused rat liver and significantly caused chloresis by increasing the bile acid independent flow (BAIF) (86). In human research, a hydroethanolic extract containing Chelidonium majus had choleretic activity by increasing the flow of bile (47).
  • CNS depressantsCNS depressants: In rats and mice, intraperitoneal administration of UkrainT potentiated the action of hexobarbital. In rats, intraperitoneal administration of UkrainT potentiated the action of amphetamine and apomorphine, but did not affect the action of haloperidol (7).
  • CNS stimulantsCNS stimulants: In rats and mice, intraperitoneal administration of UkrainT potentiated the action of hexobarbital. In rats, intraperitoneal administration of UkrainT potentiated the action of amphetamine and apomorphine, but did not affect the action of haloperidol (7).
  • Cytotoxic agentsCytotoxic agents: UkrainT exhibits toxicity toward malignant cells. Some experts have presented evidence that UkrainT is equally toxic to normal, transformed, and malignant cell lines (36; 33). Treatment of peritoneal exudates macrophages from tumor bearing mice with Ukrain restored their defective cytolytic response against DA-3 tumor cells. This data suggests that the in vivo anti-tumor effects of Ukrain may be due in part it its ability to restore the cytolytic function of macrophages (66).
  • Dopamine agonistsDopamine agonists: Research with intraperitoneal administration of UkrainT in rats has shown that one of the primary actions of UkrainT involves stimulation of the dopaminergic system (7).
  • Dopamine antagonistsDopamine antagonists: Research with intraperitoneal administration of UkrainT in rats has shown that one of the primary actions of UkrainT involves stimulation of the dopaminergic system (7).
  • Gastrointestinal agentsGastrointestinal agents: In vitro, STW 5 (Iberogast?), which contains extracts from the plants Iberis amara, Melissa officinalis, Matricaria recutita, Carum carvi, Mentha x piperita, Glycyrrhiza glabra, Angelica archangelica, and Silybum marianum, relaxed the proximal stomach but increases antral motility (87). Several of the individual extracts were found to relax the proximal stomach, while others including celandine increased motility of the proximal stomach. All extracts increased motility in the antrum in the manner of STW 5.
  • ImmunosuppressantsImmunosuppressants: The immunomodulating effects of UkrainT include improvements in total T-cell, T-helper cell, and NK-cells counts, a decrease in T-suppressor cells, and a normalizing of the H/S ratio in cancer patients (37; 35). In human research, Chelidonium majus improved immune responses and decreased disease recurrences in children with persistent tonsillitis, though statistical significance was unclear (47).
  • InterferonsInterferons: In in vitro research, the combination of greater celandine and recombinant interferon-gamma (rIFN-gamma) resulted in a marked cooperative induction of nitrous oxide (NO) production and a significant increase in tumor necrosis factor-alpha (TNF-alpha) in mouse peritoneal macrophages (12).
  • Osteoporosis agentsOsteoporosis agents: UkrainT, administered intraperitoneally at doses of 7 or 14mg/kg (every other day for 10 days, followed by a 10-day break, for five cycles), resulted in decreased bone mineral density in ovariectomized rats, as assessed by the dual-energy X-ray absorptiometry (DXA) densitometric method (69). In theory, greater celandine or UkrainT may interact with osteoporosis agents.
  • Serotonin receptor antagonistsSerotonin receptor antagonists: Research with intraperitoneal administration of UkrainT in rats has shown that one of the primary actions of UkrainT involves inhibition of the serotonergic system (7).

    • Greater celandine/Herb/Supplement Interactions:

  • AnalgesicsAnalgesics: In a prospective multicenter pilot study Cholagogum F Nattermann? (dried extracts of Scholkraut and Curcuma) reduced right upper quadrant colicky pain more effectively than placebo in 76 patients with biliary dyskinesia (1).
  • Antibacterial agentsAntibacterial agents: In a systematic review evaluating in vivo, in vitro, and animal research, Chelidonium majus has been reported to be one of the most active antimicrobial plants with antibacterial activity against S. aureus, Bacillus cereus, multiresistant Enterococci (47). In animal research, UkrainT administered subcutaneously to balb/C mice had effects on E. coli and S. aureus (78; 79). Researchers also report that lectins from Chelidonium majus L. (CML) have demonstrated potent antimicrobial properties against multiresistant Enterococci and Staphylococci (80).
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): The major alkaloids from plants such as greater celandine and drugs such as "UkrainT" (thiophosphoric acid derivative of a sum of the alkaloids isolated from greater celandine) have been shown to be irreversible inhibitors of the oxidative deamination reaction of serotonin and tyramine catalyzed by rat liver mitochondrial monoamine oxidase (MAO) (8). Chelironine and the drug UkrainT were the strongest inhibitors of the reaction among the agents studied.
  • Antidepressants, selective serotonin reuptake inhibitors (SSRIs)Antidepressants, selective serotonin reuptake inhibitors (SSRIs): Research with intraperitoneal administration of UkrainT in rats has shown that one of the primary actions of UkrainT involves inhibition of the serotonergic system (7).
  • Antifungal agentsAntifungal agents: In a systematic review evaluating in vivo, in vitro, and animal research, Chelidonium majus has been reported to be one of the most active antimicrobial plants with antifungal activity against Candida albicans, Fusarium oxysporum, and Botrytis cinerea (47). Aqueous extracts of Chelidonium majus L. demonstrated considerable inhibitory action against 10 Fusarium strains. However, methanolic extracts showed the best results. Root extracts showed more powerful growth inhibition than shoot extracts. Since most Fusarium strains have high resistance to conventional fungicides, the authors proposed Chelidonium majus as a good source of constituents valuable for the treatment of Fusarium fungal infections (81).
  • Anti-inflammatoriesAnti-inflammatories: In a systematic review evaluating animal research in mice, Chelidonium majus extract suppressed arthritis by decreasing production of TNF-alpha, interleukin-6, interferon-gamma, B cells, and gamma delta T cells (47). According to a laboratory study, stylopine, a major constituent of Chelidonium majus L. leaf, suppresses nitrous oxide (NO) and prostaglandin E2 (PGE2) production in macrophages by inhibiting the iNOS and COX-2 expressions (24). These biological activities of stylopine may contribute to the anti-inflammatory activity of Chelidonium majus. It has also been proposed that quaternary benzophenanthridine alkaloids from Chelidonium majus may play a role in the anti-inflammatory activity (10).
  • AntineoplasticsAntineoplastics: UkrainT exhibits toxicity toward malignant cells. Some experts have presented evidence that UkrainT is equally toxic to normal, transformed, and malignant cell lines (36; 33; 54). In theory, greater celandine or UkrainT may have additive effects with herbs with potential anticancer effects. In in vitro research, UkrainT induced apoptosis in a panel of cancer cell lines (including HeLa cervical cancer cells) through activation of the intrinsic cell death pathway (82). Systematic reviews have reported that UkrainTM (alkaloids from Chelidonium majus conjugated with thiophosphoric acid) may have less adverse effects and some benefit in breast, bladder, rectal and colorectal, pancreatic cancers, and Kaposi sarcoma vs. conventional anticancer medications (47) and that use of UkrainT to treat cancer is supported by many clinical and pre-clinical trials in a range of malignancies; however, many of the studies had methodological limitations (57).
  • Antispasmodic agentsAntispasmodic agents: Chelidonium majus extract demonstrated weak antispasmodic activity against acetylcholine (ACh)-induced contraction on isolated rat ileal smooth muscle (16). In another study, two ethanolic dry extracts from Chelidonium majus L. (one with a defined content of the main alkaloids (chelidonine, protopine, and coptisine) and one with the alkaloids themselves) demonstrated antispasmodic effects on isolated ileum of guinea-pigs (84). Chelidonine and protopine exhibited the known papaverine-like musculotropic action, whereas coptisine (up to 3.0 x 10-5g/mL) was ineffective in the BaCl2-stimulated ileum. All three alkaloids antagonized carbachol and electric field stimulated contractions.
  • Antiulcer agentsAntiulcer agents: Based on animal study, Chelidonium majus extract alone and in a combination with extracts from the plants Iberis amara, Melissa officinalis, Matricaria recutita, Carum carvi, Mentha x piperita, Glycyrrhiza glabra, Angelica archangelica, and Silybum marianum (STW 5 (Iberogast?) produced a dose dependent anti-ulcerogenic activity against indometacin induced gastric ulcers in rats (28).
  • AntiviralsAntivirals: A substance isolated from the freshly prepared crude extract of Chelidonium majus L. has been shown to have antiretroviral activity against HIV-1 in vitro (83). Various components of UkrainT have reported inhibitory effects on grippe virus of A type (England) 42/72 (H3N2) in Swiss albino mice, and these substances include the totality of Chelidonium majus alkaloids, thiophosphamide (the alkalizing agent), the sum of alkaloids modified by thiotepa, and some other alkaloids as their alkalized derivatives (85).
  • Choleretic agentsCholeretic agents: The total ethanolic extract of Chelidonium majus L. were tested for their choleretic activity using the isolated perfused rat liver and significantly caused chloresis by increasing the bile acid independent flow (BAIF) (86). In human research, a hydroethanolic extract containing Chelidonium majus had choleretic activity by increasing the flow of bile (47).
  • CNS depressantsCNS depressants: In rats and mice, intraperitoneal administration of UkrainT potentiated the action of hexobarbital. In rats, intraperitoneal administration of UkrainT potentiated the action of amphetamine and apomorphine, but did not affect the action of haloperidol (7).
  • CNS stimulantsCNS stimulants: In rats and mice, intraperitoneal administration of UkrainT potentiated the action of hexobarbital. In rats, intraperitoneal administration of UkrainT potentiated the action of amphetamine and apomorphine, but did not affect the action of haloperidol (7).
  • Cytotoxic agentsCytotoxic agents: UkrainT exhibits toxicity toward malignant cells. Some experts have presented evidence that UkrainT is equally toxic to normal, transformed, and malignant cell lines (36; 33). Treatment of peritoneal exudates macrophages from tumor bearing mice with Ukrain restored their defective cytolytic response against DA-3 tumor cells. This data suggests that the in vivo anti-tumor effects of Ukrain may be due in part it its ability to restore the cytolytic function of macrophages (66).
  • Dopaminergic agentsDopaminergic agents: Research with intraperitoneal administration of UkrainT in rats has shown that one of the primary actions of UkrainT involves stimulation of the dopaminergic system (7).
  • Gastrointestinal agentsGastrointestinal agents: In vitro, STW 5 (Iberogast?), which contains extracts from the plants Iberis amara, Melissa officinalis, Matricaria recutita, Carum carvi, Mentha x piperita, Glycyrrhiza glabra, Angelica archangelica, and Silybum marianum, relaxed the proximal stomach but increases antral motility (87). Several of the individual extracts were found to relax the proximal stomach, while others including celandine increased motility of the proximal stomach. All extracts increased motility in the antrum in the manner of STW 5.
  • HypoglycemicsHypoglycemics: Greater celandine has traditionally been used for the treatment of diabetes; however, administration of dried leaves of celandine (6.25% of diet by weight) to streptozotocin induced diabetic rats did not affect the development of hyperphagia polydipsia, body weight loss, hyperglycemia, or hypoinsulinemia (20).
  • ImmunomodulatorsImmunomodulators: The immunomodulating effects of UkrainT include improvements in total T-cell, T-helper cell, and NK-cells counts, a decrease in T-suppressor cells, and a normalizing of the H/S ratio in cancer patients (37; 35). In human research, Chelidonium majus improved immune responses and decreased disease recurrences in children with persistent tonsillitis, though statistical significance was unclear (47).
  • Neurologic agentsNeurologic agents: In rats and mice, intraperitoneal administration of UkrainT potentiated the action of hexobarbital. In rats, intraperitoneal administration of UkrainT potentiated the action of amphetamine and apomorphine, but did not affect the action of haloperidol (7).
  • Osteoporosis agentsOsteoporosis agents: UkrainT, administered intraperitoneally at doses of 7 or 14mg/kg (every other day for 10 days, followed by a 10-day break, for five cycles), resulted in decreased bone mineral density in ovariectomized rats, as assessed by the dual-energy X-ray absorptiometry (DXA) densitometric method (69). In theory, greater celandine or UkrainT may interact with herbs with effects on bone density.
  • TurmericTurmeric: Several weeks after ingesting a combination herbal preparation containing greater celandine (Chelidonium majus) and curcuma root, a 42 year-old woman developed jaundice due to acute hepatitis (27). Her clinical recovery was rapid after withdrawal of the medication, and within two months her hepatic functions had returned to normal. This report raises the question of a possible interaction between greater celandine and curcuma root; however, causality remains unclear.

    • Greater celandine/Food Interactions:

  • Insufficient available evidence.

    • Greater celandine/Lab Interactions:

  • AlbuminAlbumin: UkrainT has been shown to lower the anti-ovalbumin IgE antibody response and decrease antigen-induced histamine release from mast cells in ovalbumin (OA) sensitized mice (88).
  • Amino acidsAmino acids: In human research, NSC-631570 induced changes in serum amino acids (89). Changes that were reported were effects on amino acids with positively charged (histidine, arginine) and not charged (tyrosine, threonine, glutamine) R-groups, and a decrease in the concentrations of histidine and an increase in the concentrations of beta-alanine and taurine.
  • Body weightBody weight: Treatment with UkrainT in ovariectomized rats resulted in an increase in body weight (41).
  • Bone densityBone density: UkrainT, administered intraperitoneally at doses of 7 or 14mg/kg (every other day for 10 days, followed by a 10-day break, for five cycles), resulted in decreased bone mineral density in ovariectomized rats, as assessed by the dual-energy X-ray absorptiometry (DXA) densitometric method (69).
  • Immune markersImmune markers: The immunomodulating effects of UkrainT include improvements in total T-cell, T-helper cell, and NK-cells counts, a decrease in T-suppressor cells, and a normalizing of the H/S ratio (37; 35). In human research, Chelidonium majus improved immune responses and decreased disease recurrences in children with persistent tonsillitis, though statistical significance was unclear (47).
  • Liver enzymesLiver enzymes: According to reviews, ingestion of Chelidonium majus elevated liver function tests such as serum aminotransferase; however, tests normalized after a few months of discontinuation (47; 50).
  • Serum glucose levelsSerum glucose levels: Greater celandine has traditionally been used for the treatment of diabetes; however, administration of dried leaves of celandine (6.25% of diet by weight) to streptozotocin induced diabetic rats did not affect the development of hyperphagia polydipsia, body weight loss, hyperglycemia, or hypoinsulinemia (20).