| The plant Potentilla anserine L.,affiliated to Rosaceae Potentilla,is a perennial herb with creeping stolons.Its tuberous roots have been used frequently as a folk medicine and were contained in the drug standards of Qinghai Province in 1992.Potentilla anserine L.,also known as“Zhuoma”,“ginseng fruit”and“Zhuolao Shaseng”in Tibetan,is widely distributed in the western areas of China,particularly in extremely cold or high altitude areas such as Gansu,Qinghai,and Tibet.For thousands of years,it has been consumed as a high valued tonic food and can be used as an ingredient to make snacks and beverages.Additionally,the tuberous roots of this plant also have been applied in herbal medicine promoting fluid,relieving thirst,warming the stomach,strengthening the spleen,invigorating the blood and so on.Rich chemical constituents of P.anserine,such as polysaccharides,triterpenes and triterpene glycosides,flavonoids and flavan-3-ols,tannins,furanocoumarins,and phenolic acids have been reported.In addition,modern pharmacological studies have revealed that the tuberous roots have multiple bioactivities,such as anti-oxidation,anti-aging,anti-inflammatory,antihyperlipidemic,hepatoprotective,and immunomodulatory activities.In order to illustrate the bioactive components of P.anserine,a phytochemical study was conducted systematically.We deals with the isolation using various separation techniques,such as extraction,vacuum silica gel column chromatography,ODS column chromatography,Sephadex LH-20 gel column chromatography,high pressure rapid preparative chromatography,and semi-preparative liquid chromatography and nineteen pure compounds have been obtained from the ethyl acetate fraction or n-butyl alcohol fraction of P.anserine.Their structures were elucidated by chemical properties and spectrophotography analysis?NMR,MS?.Among them,two new compounds were found,and ten were firstly found from this genus.The results are as follows:crotonine?PL-1?,quercetin-3-O-?-L-rhamnopyranosyl-?1?6?-?-D-glucopyranosyl?PL-2?,rosamultin?PL-3?,kaii-ichigeside F1?PL-4?,arjunetin?PL-5?,fupanzic acid?PL-6?,ginsenosides-Rg1?PL-7?,cecropiacic acid 3-methyl ester?PL-8?,2-oxopomolic acid?PL-9?,oxopomolic acid?PL-10?,dehydrodigallic acid monomethyl ester?PL-11?,p-hydroxybenzoic acid?PL-12?,methyl gallate?PL-13?,dehydrodigallic acid dimethyl ester?PL-14?,?+?-cycloolivil?PL-15?,?+?-lyoniresinol?PL-16?,?+?-cycloolivil?PL-17?,3-methoxylonicerinol?PL-18?,?7?,8?,8'??-4-?4-hydroxy-3-methoxyphenyl?-4-hydroxy-2-?4-hydroxy-3-methoxyphenyl?-3-hydroxymethyltetrahydrofuran?PL-19?.The compounds of PL-1,PL-2,PL-6,PL-7,PL-8,PL-11,PL-14,PL-15,PL-16,and PL-17 were firstly isolated from the genus Potentilla,PL-18 and PL-19 are new compounds.It is documented that rosamultin is a active monomers isolated from P.anserine,which has the ability to scavenge oxygen free radicals,improve the function of mitochondria,and inhibit apoptosis.In this paper,rosamultin was separated and enriched by high pressure rapid preparative chromatography from P.anserine,to provide the material basis for the further pharmacological research.Cisplatin?CDDP?is a highly effective chemotherapeutic drug used for the treatment of various solid tumors for many years.However,the severe side effects of cisplatin,especially to nephrotoxicity,limit its clinical applications.Excessive production of free radicals and lipid peroxidation has been found in cisplatin-induced renal dysfunction,which can activate multiple pro-inflammatory cytokine responses and cause irreversible renal damage.The researchs suggested that oxidative stress and inflammation might play critical roles in the pathogenesis of cisplatin-induced nephrotoxicity.Therefore,antioxidants might be potential candidates for preventing and treating cisplatin-induced nephrotoxicity.In the present study,rosamultin was selected to explore its protective effects and possible molecular mechanisms in preventing cisplatin-induced acute nephrotoxicity.In vitro,the efficacy of rosamultin was evaluated using a HEK-293 T cellular model.MTT assay showed that rosamultin could significantly decrease the toxicity of cisplatin in a dose-dependent manner.Cell viability was reduced to 59.9%,in 100?M cisplatin group.At a concentration of 25?M,rosamultin improved the cell viability to 78.06%?0.001<P<0.01?.In addition,flow cytometry was used to detect changes of intracellular ROS levels.Compared with 100?M cisplatin group,rosamultin at the concentration of100?M dramatically decreased intracellular ROS levels with the inhibitory rate of32.58%.The results suggested that its mechanisms against cisplatin-induced nephrotoxicity might through scavenging free-oxygen radicals.In vivo,cisplatin-induced acute renal failure was performed in male Balb/c mice.Detected by blood biochemical criterion,the levels of Urea,Crea,CK,ALT and AST in mice treated by rosamultin(12 mg·kg-1)were significantly decreased compared with cisplatin(15mg·kg-1,i.p.)group.Finally,models of S180 sarcoma mice were used to observe the assistant anti-tumor activity effect of rosamultin on S180 tumor mice.Our findings suggested that administering rosamultin(12 mg·kg-1)with cisplatin might alleviate the associated nephrotoxicity without compromising its therapeutic efficiency.The results of this research enriched material base exploration of chemical constituents from the tuberous roots of P.anserina.At the same time,it provided a novel potential strategy in the clinical treatment of cancer. |
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