Regulation of chronic proliferative inflammation by drugs was reviewed with special reference to collagen metabolism which is an important inflammatory reaction in the proliferative phase of inflammation. An animal inflammation model, called"the carrageenin-air-pouch inflammation in rats, "is an excellent model for the chronic proliferative inflammation. Collagen in the granulation tissue induced by carrageenin is mainly types I and III collagens. The half-life of collagen is about 3.5 d in granulation tissue, indicating that the collagen breakdown in the proliferative inflamed tissue is very rapid compared with that in normal tissues, in which the half-life of collagen is about 60-70 d. This rapid breakdown of collagen may occur both extra-and intra-cellularly by proteinases such as collagenase, gelatinase and cathepsin B. On the basis of the results of experiments using proteinase inhibitors, it is suggested that a neutral proteinase (s) which activates a latent collagenase plays an important role in the rapid breakdown of collagen in granulation tissue. Anti-inflammatory steroids suppress and β-aminopropionitrile enhances the collagen breakdown in granulation tissue, though the mechanism is unclear at the present time. Inhibitory effect of anti-inflammatory steroids on collagen synthesis is significantly greater than that on the synthesis of noncollagen protein in granulation tissue. This greater inhibition of collagen synthesis by the steroids is due to a strong inhibition of procollagen synthesis without affecting the hydroxylation of procollagen, the precursor of collagen. On the other hand, D-penicillamine inhibits the hydroxylation of procollagen by chelating ferrous iron, a cofactor of prolyl hydroxylase, resulting in the selective inhibition of collagen synthesis. In addition, a strong inhibition of collagen synthesis by the steroids is discussed in connection with the steroid-induced inhibition of the deoxyribonucleic acid synthesis in granulation tissue. Two modes of drug action for the enhanced resorption of the pre-formed granulation tissue can be considered ; one is"suppression type"of drugs such as anti-inflammatory steroids which inhibit collagen breakdown and the syntheses of collagen and noncollagen protein, and the other is"enhancement type"of drugs such as CaEDTA and progesterone which increase the degradation of noncollagen protein only.
Half-waves (E1/2) of polarogram of some aromatic ketones were measured. By use of the simple HMO, it was found that the lowest unoccupied MO (LUMO) energy is well correlated with the E1/2. From the correlation between the LUMO energy and the E1/2, the conformation of neutral molecules of some thermochromic ethylenes in solution and the origin of conformational change were estimated.
In the consecutive examination of stereoselective reduction of 2-aminoketones, amine borane reduction of both their free bases and hydrochlorides afforded stereoselectively the corresponding erythro-alcohols.
The alkaloidal constituents of Aconitum yesoense NAKAI was reinvestigated. In addition to the reported constituents, i.e. kobusine, pseudokobusine, lucidusculine, neoline, chasmanine, mesaconitine, and jesaconitine, two known compounds, luciculine and aporphine type alkaloid, glaucine, were isolated. Furthermore, six new bases, i.e. 1-acetylluciculine, 14-acetylneoline, pyrochasmanine, ezochasmaconitine, anisoezochasmaconitine, and ezochasmanine, were isolated and their structures were elucidated. Ezochasmaconitine and anisoezochasmaconitine were deduced to be 8-benzoyl-14-acetylchasmanine and 8-anisoyl-14-acetylchasmanine from the spectroscopic studies, and they were synthesized from chasmanine, respectively. These two bases are the first examples of the diterpene alkaloids possessing the aroyl groups at C-8 and acetyl group at C-14. Ezochasmanine was proved to be 3-α-hydroxychasmanine on the basis of spectral analyses of the parent material and acetyl derivatives, and on the derivation to the known diterpene alkaloid, chasmanine.
A simple and rapid high-performance liquid chromatographic (HPLC) procedure was established for the quantitative determination of swertiamarin in compound of pharmaceutical preparations including swert. Herb. Pulv. Swertiamarin was extracted with water from pharmaceutical pharmaceutical preparations, cleaned up through SEP-PAK C18[○!R] cartridge and analyzed by HPLC. Swertiamarin was separated with a mobile phase of H2O-CH3CN (9 : 1) mixed solution on Nucleosil 10C18 column. Stability of swertiamarin in pharmaceutical preparations was also investigated. It was concluded that the combination of Swert. Herb. Pulv. with antacids accelerated the decomposition of swertiamarin, and that with crude drugs and digestive enzymes did not give any significant influence. The decomposition behavior of swertiamarin in aqueous solution was studied to be pseudo first order reaction.
The application of numerical analysis is suitable for the estimation of rate constant of dissolution and the simulation of dissolution under nonsink conditions. The dissolution rate constants of various particle sizes of methyl-, ethyl-, propyl-, butylparaben were calculated by the numerical analysis, and it was clarified that the product of dissolution rate constant by particle size is nearly equal for all experiments and that the dissolution rate constants do not change under both sink and nonsink conditions. The effects of solubility, nonsink condition, crystal size and crystal shape on dissolution rate were simulated.
The effect of furanogermenone was investigated on experimental liver damage induced by the administration of CCl4, d-galactosamine, ethionine, thioacetamide, phalloidin and α-amanitin. Furanogermenone suppressed the increase of serum GOT and GPT induced by CCl4, but it proved to have no significant effect on other hepatotoxins.
Fungistatic effects of forty acetylenic compounds on Trichophyton asteroides were examined in vitro. Among these compounds, propiolic acid (β-naphthyl) methyl ester was demonstrated to have more potent fungistatic activity than pentachlorophenol, a reference compound. There results indicate a fungistatic activity comparable to Haloprogin which is clinically used as a chemotherapeutic drug of dermatomycosis.
Artemisiae capillaris FLOS is one of the oldest Chinese medical plants as antiinflammatory, antipyretic, choleretic and diuretic agants in the case of liver disorder and yellow disease. In order to clarify the pharmacological significant substances in this plant, some pharmacological activities, especially antiinflammatory (Whittle's method, carrageenin edema, thermal edema) and analgesic (Whittle's method, hot-plate method, Haffner's method) effects were examined in mice and rats. A main coumarin derivative in A. capillaris, 6, 7-dimethylesculetin, showed antiinflammatory, analgesic and choleretic properties. It can be assumed that the measurement of 6, 7-dimethylesculetin content is one of the parameter for the evaluation of this crude drug.
From the n-BuOH soluble fraction of aqueous extract of roots of Stellaria dichotoma L. var. lanceolata BGE., two new C-glycosylflavonoids were isolated. The chemical structures of these compounds were established as 6, 8-di-C-galactopyranosylapigenin and 6-C-galactopyranosylisoscutellarein, respectively, by chemical and physical analyses.
Syntheses of 4-alkoxyimino (or alkylaminomethylene)-3-methylcarbamoyl-1-methyl (or phenyl)-2-pyrazolin-5-ones were carried out to test their analgesic activity. The reaction of 3-ethoxycarbonyl-1-methyl (or phenyl)-5-hydroxypyrazole (Ia, b) with sodium nitrite in hydrochloric acid or acetic acid gave 3-ethoxycarbonyl-4-hydroxyimino-1-methyl (or phenyl)-2-pyrazolin-5-one (IIIa, b), which were converted to amides (Va, b). The reaction of Ib with N, N'-diphenylformamidine in acetic anhydride gave 4-anilinomethylene-3-ethoxycarbonyl-1-phenyl-2-pyrazolin-5-one (VII), whose reaction with 30% methylamine methanol solution gave 4-anilinomethylene-3-methylcarbamoyl-1-phenyl-2-pyrazolin-5-one (VIII) (9.4%) and 4-(N-methylaminomethylene)-3-methylcarbamoyl-1-phenyl-2-pyrazolin-5-one (IX) (64.9%). VIII showed analgesic activity in mice.
The whole plants of Solanum nigrum L. (Solanaceae) has been used to treat cancer in combination with other herbs in Shanghai, China. From the immature berries of this plant, five steroidal glycosides, SN-0 (I), SN-1 (II), SN-2 (III), SN-3 (IV) and SN-4 (V) have been isolated and the former four were characterized as 26-O-(β-D-glucopyranosyl)-22-methoxy-25D-5α-frost-3β, 26-diol 3-O-β-lycotetraoside, desgalactotigonin, solamargine and solasonine, respectively. In addition, effects of I, II, III and IV on JTC-26 have been examined and it has been suggested that II, III and IV possess inhibitory activity against JTC-26 (100, 97.9, 100%, respectively, in a concentration of 15 μg/ml) and I has no activity.
Measurement of thiopental sodium-induced sleepig time was carried out as a parameter for the determination of the effectiveness of antihepatotoxic substances on liver damage induced by carbon tetrachloride. New sesquiterpenoid"Furanogermanone"isolated from the hexane extractive of "Zedoariae Rhizoma (on the goods from China)"prevented the prolongation of the sleeping time in mice caused by the administration of CCl4 and the increase in serum GOT, GPT and LDH levels.
Two new C-methyl flavanones, named matteucin (III) and methoxymatteucin (IV) were isolated from the root of Matteuccia orientalis TREV. (Aspidiaceae), together with the known desmethoxymatteucinol (I) and matteucinol (II). The structures of these flavanones were determined to be (2S)-5, 7, 2'-trihydroxy-6, 8-dimethylflavanone and (2S)-5, 7, 2'-trihydroxy-5'-methoxy-6, 8-dimethylflavanone, respectively, by spectroscopic evidence.