Розмарин и рак Rosmarinus officinalis & cancer Научные исследования
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- 7. Concluding Remarks
7. Carnosol Safety and ToxicityIn the Ames Salmonella tester strain TA102 carnosol was found to have significant antioxidant activity with anti-mutagenic activity similar to ascorbic acid [52]. Several studies have suggested that carnosol is protective against environmental toxins in experimental animal models of hepatotoxicity [53–55], bronchial cells [56], and may assist in inducing phase II detoxification enzymes [57]. In the micronucleus test for mutagenesis carnosol was found to be more effective than L-ascorbic acid for gamma-ray radioprotection capacity both before and after radiation exposure [58]. Several animal studies have suggested that daily oral administration of carnosol is well tolerated. In our study, we observed that oral administration of carnosol at 30 mg/kg was well tolerated when administered five days weekly over a 28 day period as evidenced by daily body weight measurements which did not vary between carnosol or vehicle treated mice [9]. In another study, Sprague-Dawley rats were administered an AIN-76A diet with up to 1% carnosol for two weeks with no observable effects on body weight [44]. In a separate experiment with the same group carnosol at 200 mg/kg administered intraperitoneally for five consecutive days was well tolerated as evidenced by measuring liver weight. C57BL/6J/Min/+ (Min/+) Mouse were administered carnosol up to 0.1% in their daily diet was well tolerated over a ten week period [50]. As an alternative approach, future studies should consider evaluating highly characterized rosemary extracts that are standardized to carnosol. This strategy has been employed for studying EGCG (epigallocatechin-3-gallate) in clinical trials through the use of a highly characterized green tea extract standardized to EGCG and other green tea polyphenols [1]. This approach has been recognized by the FDA as seen in their guidance titled, “Guidance for Industry – Botanical Drug Products” and by botanical products receiving investigational new drug (IND) status such as Polyphenon E. The benefit of using a highly characterized extract would be cost to procure carnosol would be cheaper because less purification would be required. A second benefit could be that additional constituents that are found in rosemary would have the opportunity to work synergistically with carnosol. Further studies are needed to evaluate highly characterized rosemary extracts standardized to carnosol. Recently, the European Union has approved a rosemary extract standardized to carnosol for its application towards food preservation and has been adopted into the EU food additive legislation [59]. This extract was well tolerated in short and long term toxicity studies. In a 13 week oral study in male and female rats the NOAEL (no observable adverse event level) of different rosemary extracts was between 180 to 400 mg/kg/bw/day which was equivalent to 20–60 mg/kg /day of carnosol and carnosic acid per day. The adult mean intake of this extract was estimated to be between 500 and 1500 mg of carnosol and carnosic acid per day. Further studies are needed to determine the anti-cancer properties of these rosemary extracts in addition to evaluating isolated constituents from rosemary. 7. Concluding RemarksThe bioavailability and metabolism of carnosol in either animals or humans has not been investigated. The bioavailability of carnosic acid, which shares structural similarities to carnosol are summarized briefly [60]. The Cmax of carnosic acid was 128 µM (42.52 mg/L) when administered intragastrically at 90 mg/kg and the absolute bioavailability of carnosic acid was 65.09%. These results are promising suggesting that diterpenes are well absorbed, however, further studies are needed to determine if carnosol has similar pharmacokinetic parameters to carnosic acid. Pharmacokinetic studies of carnosol will be critical in determining the potential use of carnosol for application as an anti-inflammatory and anti-cancer agent. Several pre-clinical studies have suggested that carnosol selectively targets tumorigenic cell as opposed to non-tumorigenic cells and is safe and tolerable in animals. Further studies are needed to understand molecular interactions of carnosol with deregulated pathways associated with inflammation and cancer. To understand the full potential of carnosol as a chemopreventive or chemotherapeutic agent more mechanistic studies are needed. Фармакология розмарина (Rosmarinus officinalis Linn.) и его терапевтический потенциал. Использование растений так же стара, как человечество. Натуральные продукты дешевые и утверждал, чтобы быть безопасным. Они также являются подходящим сырьем для производства новых синтетических препаратов. Розмарин (Rosmarinus officinalis Linn.) это обычные бытовые растение выращивается во многих частях мира. Он используется для ароматизатор пищевой, напиток, пить, а также в косметике; в народной.в медицине он используется как антиспазматическое в почечной колики, дисменорея, в освобождении дыхательных расстройств и стимулировать рост волос. Экстракт розмарина расслабляет гладкую мускулатуру трахеи и кишечника, оказывает желчегонное, гепатопротекторное и antitumerogenic деятельности. Самых важных составляющих розмарина являются кофейной кислоты и ее производные, такие как розмариновая кислота. Эти соединения обладают антиоксидантным действием. В фенольные соединения, розмариновой кислоты, получает один из его фенольных колец из фенилаланина с помощью кофейной кислоты, а другой-из тирозина через dihydroxyphenyl-молочная кислота. Относительно крупное производство розмариновой кислоты может быть получен из культуры клеток Coleus blumei Benth при поставке с экзогенно фенилаланин и тирозин. Розмариновая кислота хорошо всасывается из желудочно-кишечного тракта и кожи. Он повышает выработку простагландина Е2 и уменьшает выработку лейкотриенов B4 в человеческих полиморфно-ядерных лейкоцитов, и тормозит систему комплемента. Делается вывод, что Розмари и ее трехсторонних участников, особенно производные кофейной кислоты, такие как розмариновая кислота имеют терапевтический потенциал в лечении или профилактике бронхиальной астмы, спазмогенную расстройства, язвенная болезнь желудка, воспалительные заболевания, гепатотоксичность, атеросклероз, ишемическая болезнь сердца, катаракта, рак и плохой подвижности сперматозоидов. Indian J Exp Biol. 1999 Feb;37(2):124-30. жүктеу/скачать 2.03 Mb. Достарыңызбен бөлісу:
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