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Pancreatic cancer (PC) is one of the most lethal human malignancies worldwide. Here, we demonstrated that xanthohumol (XN), the most abundant prenylated chalcone isolated from hops, inhibited the growth of cultured PC cells and their subcutaneous xenograft tumors. XN treatment was found to induce cell cycle arrest and apoptosis of PC cells (PANC-1, BxPC-3) by inhibiting phosphorylation of signal transducer and activator of transcription 3 (STAT3) and expression of its downstream targeted genes cyclinD1, survivin, and Bcl-xL at the messenger RNA level, which involved in regulation of apoptosis and the cell cycle. Overall, our results suggested that XN presents a promising candidate therapeutic agent against human PC and the STAT3 signaling pathway is its key molecular target., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

The effectiveness of chalkones and derivatives as antibacterial and antifungal agents stimulated our interest in the possibility of coupling this type of compound with certain hydrazines and thiosemicarbazides to determine the potential chemotherapeutic activity of these combinations as anticancer and antimalarial agents. Accordingly, 18 hydrazine and thiosemicarbazide derivatives of alpha-methylchalkone (dypnone) have been synthesized for study as potential antitumor agents in animal tumor systems against Walker 256 carcinosarcoma (intramuscular) and leukemia L-1210 and for antimalarial activity against Plasmodium berghei in experimentally infected mice. Of the series of chalkone derivatives, significant inhibition in preliminary tests against the Walker 256 carcinosarcoma (intramuscular) rat tumor system was exhibited by alpha-methylchalkone-1,4-phthalazinediyldihydrazone and showed activity in the leukemia 1210 mouse tumor system. The guanylhydrazone of alpha-methylchalkone showed good inhibition with confirmed activity against Plasmodium berghei in experimentally infected mice.

The gastric cytoprotective action of prostaglandin E2 (PGE2) and sofalcone was studied in rats. The in vitro incorporating activity of 3H-glucosamine into the gastric macromolecular glycoproteins was examined when PGE2 (0.1 mg/kg, p.o.) or sofalcone (100 mg/kg, i.p.) was administered 5, 15 or 30 min before the oral administration of absolute ethanol. The cytoprotective effect of PGE2 against gastric mucosal damage was demonstrated 5 min after PGE2 was given orally. The cytoprotective effect by sofalcone was seen after 15 min. However, during this period, the decrease in gastric macromolecular glycoprotein synthesis induced by the ethanol damage could not be restored by pretreatment with PGE2 or sofalcone. On the other hand, the reduction in the content of the gastric macromolecular glycoproteins by the ethanol damage was found to be prevented to a significant extent by pretreatment with PGE2. The same phenomenon was also observed in the administration of sofalcone. Accordingly, PGE2 has stimulating effect on the gastric glycoproteins biosynthesis, but this effect can not be considered as the mechanism responsible for cytoprotection, if indeed a single mechanism exists. Thus, it is suggested that the adhesion or maintenance of secreted macromolecular glycoproteins to the gastric tissue is closely related to cytoprotection.

In a randomized double blind study, 50 patients suffering from trunk or branch varicosis were orally treated with either a commercial preparation of Ruscus extract, trimethyl hesperidine chalcone and ascorbic acid (Phlebodril), or a placebo over 2 weeks. Changes of the venous tonus were measured by means of venous occlusion plethysmography in rest position (venous capacity, venous distensibility) as well as during (active) exercise (expelled blood volume). All parameters showed a tendency towards improvement in the verum group. The changes were partly significant (p less than 0.5). The course of the study suggests that the period of treatment possibly was too short to obtain the full pharmacologic effect.

The anti-ulcer effect of sofalcone, an isoprenyl chalcone derivative, on acetic acid-induced gastric ulcers in rats was studied histologically and histochemically. After administrations of sofalcone at 50 and 200 mg/kg twice daily for 10 days, contraction of the ulcer, mucosal regeneration, accelerated development of the collagen fibers in the granulation tissue at the base of the ulcer, and increase of acid mucopolysaccharides, an alcian blue stain-positive substance covering the regenerated mucosa, were noted. The healing effect of sofalcone was balanced in mucosal regeneration and connective tissue proliferation (formation of the collagen fibers). Sofalcone of 50 mg/kg showed a greater healing effect than gefarnate at the same dose and had a similar healing effect as L-glutamine at 200 mg/kg.

The efficacy of Essaven-capsules in venous circulatory disorders of the leg was assessed under the conditions of everyday general practice in a double blind trial including 34 out-patients. During the 4 week-treatment Essaven proved to be significantly superior to a placebo of identical appearance as regards the parameter pain in the legs, skin lesions, circumference of the ankle, and diuretic performance. The dosage was 3 X 2 capsules per day.

The ultrasound Doppler examination has proved itself to be a very promising non-invasive method for the trials of vein medication under defined test conditions. In patients with postthrombotic syndrome the medium blood stream velocity in the V. femoralis increased on the diseased side two hours after oral application of a high-dosed combination of ruscogenin, trimethyl-hesperidin-chalkon and ascorbic acid (1 X 6 capsules Phlebodril) by the mean of 24%. If one observes the quotients from the middle arterial inflow and venous outflow velocity in the femoral vessels, in order to comprehend the relation between both these necessarily correlated hemodynamic parameters, one sees that this quotient shows a decrease after medication of 40%, which was significant on the 5% level. Corresponding drug effects in the early phase after getting upright could also be proved. The importance of these results, which are from an acute trial, must still be tested in a practical long-term therapy.

Attempts were made to investigate the effect of 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy) chalcone (sofalcone) on necrotizing agents-induced gastric lesions and on prostaglandin E2 (PGE2)-like activity of the gastric tissue in rats. Sofalcone, 100 mg/kg i.p. and 300 mg/kg p.o., markedly suppressed 0.6 N HCl- or 100% EtOH-induced gastric lesions. Sofalcone, 100 mg/kg i.p., also significantly suppressed 0.2N NaOH-induced gastric lesions. Sofalcone suppressed 0.6 N HCl-induced gastric lesions with both oral and intraperitoneal routes, and the effect was particularly marked at 60 min. A dose of 100 mg/kg i.p. showed suppression lasting for up to 300 min. 0.6 N HCl-induced gastric lesions were significantly aggravated by indomethacin treatment (10 mg/kg s.c.). Oral sofalcone (300 mg/kg) significantly suppressed the aggravation of gastric lesions by indomethacin given before and after sofalcone, but the i.p. (100 mg/kg) did not show significant suppression in the case of pretreatment with indomethacin. PGs-like activity in the gastric tissue was increased in both of the fundus and the antrum by the administration of sofalcone without any dose-dependency. The increase was continuous and lasted for 6 h in the fundus of the stomach.

Ro 09-0415, a phosphorylated 'pro-drug' of the potent antirhinovirus compound, 4' ethoxy-2'-hydroxy-4, 6' dimethoxy-chalcone (Ro 09-0410) was tested in a double-blind placebo-controlled trial for its protective effect against experimental rhinovirus infection. The maximum dose, 1200 mg bd, based on considerations of practicality and tolerance was given orally both before and after challenge with a sensitive rhinovirus, type 9. Plasma concentrations of active compound in excess of those required for the inhibition of rhinovirus type 9 in vitro were achieved, but there was no evidence to suggest that treatment with Ro 09-0415 had a beneficial effect. It is concluded that Ro 09-0415 given orally is unlikely to be of value in the prophylaxis or therapy of human rhinovirus infection.

Solon, a synthetic isoprenyl flavonoid derived from sophoradin isolated from the root of an ancient Chinese plant, administered orally to rats, prevented, dose-dependently, the formation of acute gastric lesions produced by absolute ethanol given orally. Solon also enhanced the healing of chronic gastric and duodenal ulcerations induced by the serosal application of acetic acid. The gastroprotective action of Solon was probably mediated by increased mucosal content of prostaglandins (PG) due mainly to the inhibition of 15-OH-prostaglandin dehydrogenase. The ulcer-healing action of Solon was probably related to the stimulation of mucus-alkaline secretion, increased mucosal blood flow and the formation of a protective barrier on the ulcer base.

A study was made on the therapeutic effects of sofalcone (SU-88), an antiulcer agent, on erosive and atrophic gastritis induced experimentally by 6-month administration of 5 mmol/l of sodium taurocholate (TCA) in rats. A standard meal including sofalcone of 0.25% and 1.0% shortened the total length of erosions, normalized the mucosal thickness, and reduced collagenous fibers in the gastric mucosa in one month. The doses administered were 116.3 mg and 486.1 mg/kg/week for one month. Sofalcone, thus, had a good therapeutic effect on experimental erosive and atrophic gastritis in rats.

The effect of 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy)-chalcone (sofalcone, Solon) on 0.6N HCl-induced gastric lesions in the rat was studied. Sofalcone administered orally or intraperitoneally prevented the formation of gastric lesions induced by the necrotizing agent dose-dependently. Oral administration of sofalcone inhibited the aggravating effect of indometacin on the lesions induced by 0.6N HCl. Intraperitoneal administration of sofalcone also inhibited the aggravation of the lesions by indometacin treatment when it was given 30 min after the administration of sofalcone. This effect of sofalcone was not observed when indometacin was given 30 min before sofalcone. Simultaneous treatment with sofalcone and cimetidine inhibited the formation of the necrotic lesion synergistically. Carbenoxolone and cetraxate given orally protected the gastric mucosa against 0.6N HCl. Their protective effects were decreased when they were given intraperitoneally. These results suggested that the cytoprotective effect of sofalcone does not depend on the route of administration and that there are some interactions between cimetidine and sofalcone in their synergistic cytoprotective effects.