Non-Aromatic Naphthalane: A Future Remedy For Oral Mucosal Lesions

Svrha je ovoga rada prikazati podatke dobivene iz nekoliko eksperimentata koje su proveli autori u vezi sa sastavom posebne frakcije Hrvatske nafte, nazvane “NeAromatskim - Visoko Steranskim (NAVS) naftalanom, te njezinim izraženim protutupalnim djelovanjem i djelovanjem na kontrolu stanične proliferacije. NAVS je dobiven iz nafte vrlo bogate steranima, koja se desetljećima uspješno upotrebljava u liječenju psorijaze (Naftalan, Ivanić Grad, Hrvatska). Proizvodi se gotovo potpunim uklanjanjem policikličkih aromata (od kojih su neki kancerogeni), čime se dobiva potpuno bezbojno ulje ugodnoga mirisa. Prigodom postupka dearomatizaije sterani su održani i čak koncentrirani, kako je i dokazano plinskom kromatografijom i vezanim sustavom plinske kromatografije i spektrometrije masa. Ti su geogeni sterani molekularnom strukturom srodni bioaktivnim spojevima, npr. kortikosteroidima i vitaminu D. Zbog tih strukturnih sličnosti, moguće je objasniti dobru učinkovitost u liječenju psorijaze NAVS-om, u čemu su rezultati obećavajući. Tijekom liječenja NAVS-om nije bilo nikakvih promjena hematoloških niti biokemijskih nalaza. In vitro studije dokazuju izraženu dozno-ovisnu inhibiciju proliferacije stanica planocelularnoga karcinoma SCC VII, ali ne i inhibiciju nemalignih fibroblasta L929, pokazujući time selektivnost u kontroli staničnoga rasta. In vivo rezultati pokazuju znatno usporavanje rasta malignoga tumora. Uzrok tome, osim u samoj kontroli proliferacije tumorskih stanica, autori također vide i u sprječavanju neoangiogeneze (poput onom vitamina D), koje još treba dokazati imunohitokemijskim studijama. Planiraju se dodatna istraživanja i razvija se animalni model oralnog planocelularnoga karcinoma u svrhu budućeg uvođenja NAVS-a u liječenje različitih bolesti oralne sluznice budući da je NAVS i učinkovit i vrlo upotrebljiv zbog superiornih organoleptičnih svojstava.The purpose of this lecture is to summarize data obtained from several experiments conducted by authors, regarding the composition of special Croatian petrol fraction reffered to as “Non Aromatic- Very rich in Steranes” (NAVS) naphthalane, as well as its potent-inflammatory and cellular growth controlling effect. NAVS is derived from ordinary brown naphthalane, particulaly rich in steranes, that has been famous for decades in the treatment of psoriasis vulgaris (Naftalan, Ivanić Grad, Croatia). NAVS was prepared by removing virtually all of its original polycyclic aromatic content (some of them are carcinogenic), which resulted in completely colourless transparent oil with a pleasant scent. Steranes were preserved and concentrated during the de-aromatisation process, as was proven by means of GC and GC-MS. These geogenic steranes have molecular skeletons analogous to bioactive compounds, such as corticosteroids and vitamin D. Due to these structure similarities, we can explain the beneficial affects in treating psoriatic patients with NAVS, which yielded promising results. NAVS treatment did not affect either haematological or biochemical findings. Further studies established In vitro dose dependant inhibition of planocellular carcinoma (SCC VII) cell proliferation, withhout interfering with nonmalignant fibroblast (L929) cells, thus showing selectivity in cell proliferation control. In vivo results showed marked delay in tumour growth. A rationale for that, besides cell proliferation control, authors see also in the antineoangiogenetic activity of NAVS (similar to vitamin D), wich is yet to bi proved through immunohistochemical studies. Future studies are planned and oral planocellular carsinoma animal models are being developed in order to introduce NAVS in the treatment of different conditions of oral mucosa, because the preparation is not only effective, but also highly applicable in oral tissues, due to its superior organoleptic properties

Evaluation of Tanacetum larvatum for an anti-inflammatory activity and for the protection against indomethacin-induced ulcerogenesis in rats

Oral administration of the chloroform extract from Tanacetum larvatum (Griseb. ex Pant.) Kanitz caused a dose-dependent anti-inflammatory effect in the carrageenan-induced rat paw oedema test. The obtained anti-inflammatory effect was 8.6, 32.8, 37.0 and 49.5% for the extract doses of 25, 50, 100 and 200 mg/kg, respectively, being statistically significant at a dose of 50 mg/kg. Indomethacin had a strong anti-inflammatory effect of 73.4% at a dose of 8 mg/kg, but large gastric lesions were detected. When the plant extract in the highest tested dose (200 mg/kg) was concomitantly given with indomethacin, the anti-inflammatory effect was slightly enhanced, but the gastric lesions were significantly reduced. The anti-inflammatory and anti-ulcer activity may be mainly due to the inhibition of DNA binding of the transcription factor NF-kappaB by components of the plant extract. This was proven in an electrophoretic mobility shift assay at a concentration of 50 mug/ml. Due to its anti-inflammatory as well as anti-ulcer effects, Tanacetum larvatum should especially be used combined with those drugs that are known both for their strong anti-inflammatory activities and the ulcerogenic side effects such as NSAIDs

Evaluation of the anti-inflammatory and cytotoxic activities of naphthazarine derivatives from Onosma lentantha

The root extracts of Onosma leptanhtha were evaluated for their anti-iflammatory and cytotoxic activities. The cyclohexane extract, which appeared as the most active in both assays, has been further subjected to bioassay-directed fractionation to afford the naphthazarine derivatives: beta,beta-dimethylacrylshikonin (1), isovalerylshikonin (2) and acetylshikonin (3). The evaluation of the anti-inflammatory activity was performed on carrageenan-induced rat paw edema test. All the tested compounds proved to be active, while compound 3 showed the best anti-inflammatory effect. In addition, the cytotoxic activity of the extracts and isolated compounds, was also assayed against L1210 murine lymphoblastic leukemia cell line, and human fibrosarcoma HT-1080 cells. Compound I exhibited remarkable cytotoxic activity (390nM for L1210 cells), which is superior to that of shikonin, which was used as control