Quantification Of The Flavanoids In Herba Sedi Linearis And Other Two Sedum Medicines And Research On Their Antitumor Activity

Herba Sedi Linearis which originates from the whole herb of Sedum lineare Thunb.(Crassulaceae) is a kind of commonly used herbal medicine and used as an ethnicdrug to cure diseases in many minority areas of China. It was recorded to have thefunctions of clearing heat and detoxication, hemostasis, and wound healing promotionby Chinese Pharmacopoeia (1977, Volume1). And it’s also availed of to treat soreswollen throat, diversified inflammation, red eyes, dysentery, lacquer sore, herpeszoster, swollen welling-abscess, erysipelas, burn and scald, and the like. Sedi Herba,derives from the whole herb of Sedum sarmentosum Migo which is also subordinatedto genus Sedum, is the widest used medicinal drug in Sedum plants and has alreadybeen recorded by several versions of Chinese Pharmacopoeia. Tujia Minority peoplein China usually use these2Sedum plant medicines to cure of some cancers. And theirtender parts such as the leaves are always ate as vegetables in their producing areassuch as Hubei province. All of these indicate the wide therapeutic effects andmedicinal security of these2plant medicines. They possess certain development andapplication value, and deserve to be further studied. Based on the previous study ofour research group, the anticancer experiment in vitro and the antitumor mechanismstudy of their total flavones and flavonoids compounds got from Herba Sedi Linearishad been done in this research. What’s more, the contents of2flavonoids, quercetinand kaempferol, in Herba Sedi Linearis and the other2Sedum plant medicines SediHerba and Sedi Emarginati Herba (Sedum emarginatum Migo) harvested in differentseasons were simultaneously determined by High Performance LiquidChromatography (HPLC) method. This provided a new method for controlling thequality of the3crude drugs. Furthermore, their best harvest seasons had beenconfirmed.The previous research of the study group used Methye Thiazolye Telrazlium (MTT)method to test and infer that flavonoids were the major antitumor active substances inHerba Sedi Linearis, Sedi Herba and Sedi Emarginati Herba, and Herba Sedi Linearis had a better activity. To find out the definite anticancer active ingredients in HerbaSedi Linearis, MTT method was applied to detect the inhibition effects of the totalflavones in Herba Sedi Linearis and Herba Sedi, and7flavonoid compounds(Astragalin, luteolin, quecetin, and compound2,4,8,11) in Herba Sedi Linearis, andthe mixture of7compounds in accordance with the actual proportion against A549,EC109, HepG2, Accm, Vero in vitro. The result indicated that all of the ingredientsabove possessed certain and different degrees of anticancer effectiveness which waswith a dose-dependent manner in the determination content range. And compared tothe other compounds, compound2possessed a better inhibition effect against HepG2and a lower toxicity to normal cells Vero, while quecetin and compound11were bothgood at inhibiting the proliferation of A549and compound4was effective on all ofthe cancer cells. However, the anticancer effect of7compounds to each tumour cellswere almost all weaker than the total flavones in Herba Sedi Linearis or Herba Sedi.So it’s reasonable to deduce that it’s the complicated synergy among the flavonoidingredients besides these7compounds above that achieve the antitumor effect ofHerba Sedi Linearis.Further study on the inhibition effect of the antitumor active ingredients in Herba SediLinearis and Herba Sedi against Topo I (Topoisomerase I) indicated that the effect ofquecetin and compound4were better, and quercetin preferentially bound to Topo Ithus blocking the interaction between Topo I and DNA, while compound4might bindto both Topo I and DNA to restrain the activity of Topo I. These two compounds wereboth catalytic inhibitors. Furthermore, simple molecular docking experiment wasperformed to study on the inhibition mechanism at the molecular level of quercetinand compound4against Topo I. The result demonstrated once again that quercetininhibited the activity of Topo I by binding to Topo I firstly. And the docking modebetween quercetin and Topo I were also obtained.Through the simultaneous determination by HPLC of2antitumor active compoundsquercetin and kaempferol in Herba Sedi Linearis and the other2Sedum plant medicines Sedi Herba and Sedi Emarginati Herba harvested in different seasons andcombined with the results of earlier study of the group, the best harvest season of the3Sedum medicinal plants had been confirmed to be the full-bloom period between theend of April and the beginning of May. The result of this experiment also showed thatthe content of quercetin and kaempferol in all the Sedum medicinal samples harvestedin different seasons varied, and the contents of anticancer active ingredient quercetinin Herba Sedi Linearis and Sedi Herba both were higher than that in Sedi EmarginatiHerba obviously. This may be one of the reasons why the former2plant medicinespossess stronger antitumor activity.In conclusion, this research found some antitumor active substances in Herba SediLinearis and probed into their anticancer mechanism, provided significant referencesand experimental details for quality evaluation and control of Herba Sedi Linearis andthe other2Sedum plant drugs, and laid a nice foundation for exploring anddeveloping novel, efficient and safe antitumor natural medicinal resources.