Chemical constituents and their biological activities from Taunggyi (Shan state) medicinal plants.

Medicinal plants are essential aspects of readily available primary healthcare remedies. Phytochemical constituents of medicinal plants cover a broad variety of chemical fields to explore medicines. This review highlights selected empirical data on traditional uses, phytochemistry, and pharmacological properties of Taunggyi medicinal plants, Andrographis paniculata, Physalis peruviana, and Cassia fistula. Historically, these plants have been used for many infections and diseases in Taunggyi. More than 361 chemical compounds have been isolated and identified from the selected plants. Some of the chemical constituents have substantial pharmacological properties. It is clear that these herbs have significant potential for useful natural supplements in many contemporary diseases. Thus, the aim of this review compiles an ethnobotanical survey and documentation of medicinal plants in Taunggyi (Myanmar). This review will also inspire Myanmar researcher's to further investigate the potential of these plants in their future work into new compound and new drugs.

Two oleananes from Ammannia auriculata Willd.

Two new compounds: 3-ß,15-α,23,28-tetrahydroxyolean-12-en-3-O-arabinopyaranoside and 3-ß,23,28-trihydroxy-olean-12-en-3-O-ß-D-glucopyranoside were isolated from the aerial parts of Ammania auriculata along with the known compounds kaempferol, ß-sitosterol-3-O-ß- D-glucoside, 2-α,3-ß,23-trihydroxyolean-12-en-28-oic acid-28-O-ß-D-glucopyranoside, quercetin, kaempferol-3-O-α-L-arabinofuranoside, kaempferol-3-O-ß-D-xylopyranoside and ellagic acid. Structures of these compounds were elucidated on the basis of their spectroscopic data (NMR, UV, MS and IR spectra). The antioxidant activities of the total extract, the fractions CH(2)Cl(2), EtOAc and the remaining aqueous together with the compounds 1, 6 and 9 were comparable with that of the standard antioxidant, ascorbic acid.

Studies on the chemical constituents of Psoralea corylifolia L.

A new isoflavone, corylinin (1), along with six known compounds, isopsoralen (2), psoralen (3), sophoracoumestan A (4), neobavaisoflavone (5), daidzin (6) and uracil (7), have been isolated from the dried fruits of Psoralea corylifolia L. The structure of 1 was established as 7,4'-dihydroxy-3'-[(E)-3,7-dimethyl-2,6-octadienyl]isoflavone on the basis of the spectroscopic methods. Structures of the known compounds were identified by comparison of the literature.

Multiple activities of a novel substance, dictyopyrone C isolated from Dictyostelium discoideum, in cellular growth and differentiation.

We report that a novel substance named dictyopyrone C (DPC) has remarkable effects on growth and differentiation of Dictyostelium discoideum Ax-2 cells, in a dose-dependent manner. In the presence of 3-15 microM DPC, differentiation of starving Ax-2 (clone MS) cells was greatly enhanced in submerged culture, when vegetative MS cells were harvested at the mid-late-exponential growth phase (>3 x 10(6) cells per ml) and starved. In contrast, DPC above 30 microM markedly impaired the progression of differentiation including cell aggregation, most of starved cells being round after 3-4 h of DPC application and then lysed during further incubation. In the presence of 30 microM DPC however, MS cells that had been harvested at the early exponential growth phase (<5 x 10(5) cells per ml) and starved became neither round nor lysed and exhibited rather enhanced differentiation. Essentially the same results were obtained in cultures of starved cells on nonnutrient agar. With respect to the DPC effect on MS cells growing in axenic medium, cell lysis and growth inhibition by DPC at concentrations higher than 15 microM were realized in the mid-late-exponential-growth-phase cells (>3 x 10(6) cells per ml) but not in the early-exponential-growth-phase cells (<5 x 10(5) cells per ml). Moreover, analysis using synchronized MS cells has demonstrated that the DPC effect changes in a cell-cycle-dependent manner. In contrast to such unique DPC actions, the pyrone ring of DPC had no effects on growth and differentiation within the range of 3-120 microM tested. These findings strongly suggested the importance of the combined structure of the pyrone ring and the linear carbon chain in revelation of the DPC activities.

Furanodictine A and B: amino sugar analogues produced by cellular slime mold Dictyostelium discoideum showing neuronal differentiation activity.

We investigated the constituents of Dictyostelium discoideum to clarify the diversity of secondary metabolites of Dictyostelium cellular slime molds and to explore biologically active substances that could be useful in the development of novel drugs. From a methanol extract of the multicellular fruit body of D. discoideum, we isolated two novel amino sugar analogues, furanodictine A (1) and B (2). They are the first 3,6-anhydrosugars to be isolated from natural sources. Their relative structures were elucidated by spectral means, and the absolute configurations were confirmed by asymmetric syntheses of 1 and 2. These furanodictines potently induce neuronal differentiation of rat pheochromocytoma (PC-12) cells.

Isoflavonoid glycosides from Dalbergia sissoo.

Two isoflavone glycosides, biochanin A 7-O-[beta-D-apiofuranosyl-(1-->5)-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside] and tectorigenin 7-O-[beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside], were isolated from Dalbergia sissoo. Their structures were elucidated on the basis of spectral and chemical evidence.

Virol A, a toxic trans-polyacetylenic alcohol of Cicuta virosa, selectively inhibits the GABA-induced Cl(-) current in acutely dissociated rat hippocampal CA1 neurons.

The effects of virol A (VA), a toxic component of Cicuta virosa (water hemlock), on the GABA-induced Cl(-) current (I(GABA)) in acutely dissociated rat hippocampal CA1 neurons were investigated using whole-cell patch-clamp techniques. VA reversibly reduced I(GABA) and the muscimol (Mus)-induced current (I(Mus)) in a concentration-dependent manner. The IC(50) values for VA against I(GABA) and I(Mus) were 9.6x10(-7) and 9.8x10(-7) M, respectively. VA shifted the EC(50) value of I(GABA) from 6.5x10(-6) to 2.1x10(-5) M, whereas it had no effect on the maximum response, thereby suggesting that VA inhibited I(GABA) in a competitive manner. VA had no apparent effect on current-voltage relationships for I(GABA), thus indicating the lack of voltage-dependency. On the other hand, application of VA (10(-6) M) did not additionally reduce the I(GABA) suppressed by >10(-5) M picrotoxin. VA but not bicuculline accelerated the decay phase of I(GABA), as was seen with picrotoxin. Moreover, pre-application of 10(-5) M VA reduced I(GABA). VA did not inhibit that induced by glycine (10(-4) M). These results indicate that VA inhibits I(GABA) by acting both on the GABA agonist site and on the Cl(-) channel of the GABA(A) receptor-channel complex. VA is a structurally novel type of compound that selectively inhibits the GABA(A) receptor-Cl(-) channel complexes in mammalian central nervous system neurons.

In vivo subcellular elemental dynamics in liver graft: With special reference to effect of non-selective endothelin receptor antagonist, TAK-044, on the graft injury.

Background: No data are available concerning the in vivo subcellular dynamics of elements in liver grafts and the effect of endothelin receptor antagonist, TAK-044, against graft injury. Methods: Liver transplantation was performed in porcine under active veno-venous bypass. The grafts stored in chilled preservation solution were recirculated following reflush with lactated Ringer's solution with or without TAK-044 (10 mg/kg). Cold and warm ischemic times of the grafts were comparable between the two groups. Elements (Na, K, Cl, Ca, P and S) were measured in three fractions of cytoplasm, mitochondria and nucleus by electron probe X-ray microanalysis for the graft biopsy specimens obtained at various time from donor laparotomy to 1 week after liver grafting. Liver functions also were compared between the two groups. Results: In both groups, concentration of each element changed in parallel among the three subcellular fractions and their changes were less marked in the nucleus. In the control group, there were significant increases in cytoplasmic Na and Cl after portal reperfusion and in cytoplasmic and mitochondrial Ca after hepatic artery reperfusion. These were accompanied by K and mitochondrial S decreases without a statistical significance. In the TAK group, such postreperfusion elemental alterations were significantly suppressed and early deterioration of the liver functions was alleviated, as compared with the control group. Conclusion: A supplemental use of TAK-044 in a rinse solution before reflush contributed to stability of subcellular elements after reperfusion and better preservation of early graft function.

Exploring the structural basis of neurotoxicity in C(17)-polyacetylenes isolated from water hemlock.

Water hemlock, Cicuta virosa, belonging to the Umbelliferae, is well-known as a toxic plant responsible for lethal poisonings in humans as well as animals, causing tonic and clonic convulsions and respiratory paralysis. Cicutoxin (1), being a major violent toxin of the plant, is a chemical in the class of C(17)-polyacetylenes bearing a long pi-bond conjugation system, a terminal hydroxyl, and an allylic hydroxyl in its structure, and a variety of its analogues have been isolated from the plant. In the present study, various derivatives of these toxins were synthesized through acetylation, methylation, and oxidation of cicutoxin (1) and virol A (3) and B (4). 1-Dehydroxyvirol A (28) was prepared through the coupling of (7S)-dodeca-3,5-dien-1-yn-7-ol and 1-iodopentyne under Sonogashira's conditions. A monoacetylenic compound (29) was also prepared through the coupling of (5S)-1-chlorodeca-1,3-dien-5-ol and 1-iodopentyn-5-ol. The structure-activity relationships involved in the acute toxicity of cicutoxin derivatives in mice were investigated, and the length and geometry of pi-bond conjugation and the O-functional groups were found to be important for activity. The potency in inhibition of the specific binding of the noncompetitive GABA antagonist, [(3)H]EBOB, to GABA-gated Cl(-) channels of GABA receptors in rat brain cortex was found to be correlated with acute toxicity, indicating that the ability to bind to these channels plays an important role in the acute toxicity of these compounds.

Asymmetric 1,4-addition of phenylboronic acid to 2-cyclohexenone catalyzed by Rh(I)/binap complexes.

Reaction of 2-cyclohexenone with phenylboronic acid in the presence of 3 mol% of a rhodium(I)/(S)-binap catalyst in dioxane/H2O (10/1) at 100 degrees C proceeded with high enantioselectivity to give a high yield of (S)-3-phenylcyclohexanone of up to 99% ee. The high enantioselectivity was achieved by use of a catalyst generated in situ from Rh(acac)(C2H4)2 and (S)-binap or Rh(acac)((S)-binap) as an isolated rhodium-phosphine complex.

Novel acyl alpha-pyronoids, dictyopyrone A, B, and C, from Dictyostelium cellular slime molds.

For the elucidation of the diversity of secondary metabolites of Dictyostelium cellular slime molds, we investigate the constituent of three species of slime molds. From the methanol extract of their fruit bodies, we obtained three novel compounds, dictyopyrone A (1) and B (2) from D. discoideum and D. rhizoposium and dictyopyrone C (3) from D. longosporum. They possess a unique alpha-pyrone moiety with a side chain at the C-3 position. Their relative structures were elucidated by spectral means, and the absolute configuration was confirmed by asymmetric synthesis of 1. Since these compounds were obtained from different species of Dictyostelium slime molds, they may be a type of compound common to this genus.

[Biological activities of natural resources around us are now in the limelight].

There are various kind of natural resources around us, and they must contain a lot of unknown bioactive substances. Some may be structurally very strange for us, and some are very familiar. But their biological activity was not unfortunately investigated in detail. Accordingly, exploring new types of pharmaceutical resources may give lead compounds of the drugs in the future. Among those natural resources, I examined squid ink and scallop soup. From squid ink, an antitumor glycoconjugate was obtained. Its polysaccharide moieties, illexin A, illexin B and illexin C, were isolated, and the spectral data and chemical transformation of their acid hydrolysate revealed to bear a unique branched repeating unit, [-3GlcA beta 1-4(GalNAc alpha 1-3)Fuc alpha 1-]n. Moreover, scallop soup gave antitumor glycogen by the action of protease. The fine structure of glycogen was investigated by the sequential enzyme digestion method using beta-amylase and pullulanase, while the unit chain was analyzed by high performance anion exchange chromatography. The results showed that the antitumor active glycogen was highly branched with shorter chain than glycogens without antitumor activity.

[A case of Marchiafava-Bignami disease that responded to high-dose intravenous corticosteroid administration].

We report a 63-year-old male who presented acute confusional state with prominent rigidity of all extremities. The patient had a long history of alcoholism and was in poor physical condition and malnourished. The diagnosis of Marchiafava-Bignami disease was indicated by T2-weighted MRI demonstrating high signal intensity in the corpus callosum. Because Wernicke's encephalopathy was suspected as a complication, thiamine therapy was applied, but there was no clinical improvement. Immediately after high-dose intravenous corticosteroid administration was started, his symptoms rapidly resolved except for mild cognitive impairment. It is supposed that edematous change in the early stages of Marchiafava-Bignami disease causes impairment of the blood-brain barrier. Steroid therapy may prevent such a process by means of its the anti-edema effect and by normalizing blood-brain barrier. The present case suggests that corticosteroid therapy has beneficial effects for Marchiafava-Bignami disease.

New type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against Plasmodium malaria parasite.

Febrifugine (1) and isofebrifugine (2), isolated from the roots of Dichroa febrifuga Lour. (Chinese name: Cháng Shan), are active principles against malaria. Adducts of 1 and 2 with acetone, Df-1 (3) and Df-2 (4), respectively, were obtained using silica gel and acetone. They showed high activity against P. falciparum malaria in vitro. Compound 3 was found to be equally effective against P. berghei in vivo as the clinically used drug chloroquine, whereas 4 showed only 1/24 of the activity of 3. Metabolism studies of these compounds revealed that compound 4 is readily metabolized in mouse liver. Accordingly, the dose of 4 must be higher than that of 3 to attain blood levels sufficient for a favorable therapeutic effect.

Stimulation of neurotrophic factor secretion from 1321N1 human astrocytoma cells by novel diterpenoids, scabronines A and G.

Glial cells release neurotrophic factors that maintain neurons functionally. When rat pheochromocytoma cells (PC-12) were cultivated with the conditioned medium of human astrocytoma cells (1321N1) incubated with the new diterpenoids, scabronines A and G, isolated from Sarcodon scabrosus, they changed their morphology and there was neurite outgrowth. The scabronines increased the expression of mRNA for nerve growth factor (NGF), and the secretion of NGF from 1321N1 cells in a concentration-dependent manner. However, the enhanced neurite outgrowth produced by the conditioned media was slightly inhibited by NGF neutralizing antibody, and the concentration of NGF released in response to the scabronines was insufficient to cause differentiation. These results suggest that scabronines cause the secretion of other factors together with NGF from 1321N1 cells. The diterpenoids are useful drugs to clarify the mechanism of synthesis and secretion of neurotrophic factors.

Antitumor glycogen from scallops and the interrelationship of structure and antitumor activity.

Hot water extract of scallop was treated with actinase E and fractionated by Sephadex G-25 gel-filtration and DEAE Sephadex A-25 ion-exchange chromatography. The antitumor activity of these fractions against Meth-A fibrosarcoma was examined. The nonadsorbed fraction (SCA25A) and weakly adsorbed fraction (SCA25B) obtained on DEAE Sephadex A-25 anion-exchange gel showed strong antitumor activity. Chemical analyses and NMR spectra identified SCA25A and SCA25B as glycogen. However, glycogen extracted from the scallop with trichloroacetic acid and from abalone showed no antitumor activity. This difference was thought to be due to variations in the fine structure of the glycogen molecule. The fine structure of glycogen was investigated by a sequential enzyme digestion method using beta-amylase and pullulanase, while the unit chain was analyzed by high performance anion exchange chromatography. The results showed that the antitumor active glycogen was highly branched with a shorter chain than glycogens without antitumor activity.

Serial MR findings of chronic idiopathic ataxic neuropathy.

We report the case of a 70-year-old woman with chronic idiopathic ataxic neuropathy. Neurological examination, electrophysiological studies and a sural nerve biopsy suggested involvement of the axon and the dorsal root ganglia. Laboratory examination showed polyclonal elevation of serum IgA. MRI showed high signal intensity in the posterior column of the lumbar spinal cord on T2-weighted images. High signal intensity in the posterior column of the cervical spinal cord on T2-weighted images appeared during the course of the illness. MR abnormalities in this case may reflect the degeneration of the posterior column of the spinal cord subsequent to sensory ganglionic neuropathy.

Anti-tumor activity of squid ink.

The anti-tumor activity of a new type of peptidoglycan isolated from squid ink was shown to have a cure rate of 64% for Meth A tumor from BALB/c mice. The ink delipidated in acetone, which contained the peptidoglycan at 0.1% (w/w), was administered to tumor-transplanted mice so as to examine the anti-tumor activity. One-fifth of the tumor-bearing mice was cured with 3 injections (1 mg/head) of the acetone delipidated squid ink or a prolongation of survival was observed in the treated animals. Heat treatment at 100 degrees C for 10 min did not affect the anti-tumor activity of the delipidated ink, its potentiality being preserved. The acetone-extractable fraction of the ink also brought about a similar cure rate for Meth A tumor. The delipidated ink enhanced the phagocytic activity of macrophages but no direct cytotoxicity was observed for the Meth A tumor cells. Hence it may be said that the anti-tumor activity of the delipidated ink was mainly due to the augmented cellular immunity in vivo.