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The stems and leaves (SCSL) are the main byproducts of the Schisandra chinensis cultivation process, and they are worthy of research and utilization from the perspective of medicine and economic benefits. Eighteen (1–18) undescribed highly oxygenated and rearranged schinortriterpenoids (SNTs) and six analogues (19–24), including 14(13 → 12):16(17 → 13)-diabeoschiartane (1–7), 18(13 → 14)-abeoschiartanes (8–12, 19), 18-norschiartane (13), schiartanes (14, 20), 16,17-secopreschisanartanes (15–17, 21–24), lancifoartane (18) skeletons, were isolated from the SCSL. Compounds 1–7 feature a rare 7/5/5-fused carbocyclic core. The structures were established by MS, NMR, single-crystal X-ray diffraction, ECD, and biogenetic considerations. In addition, neuroprotective assays were performed to gain a preliminary understanding of their biological activity. Compounds 2, 6, and 7 showed strong neurite outgrowth-promoting activity with 13.1 %, 12.0 %, and 12.2 % cell differentiation rate (positive group: 15.4 %), respectively. Compounds 1, 2, and 11 at a concentration of 25 μM also had neuroprotective effect on corticosterone (CORT)-induced PC12 cell injury, the cell viability was increased by 21.1 %, 19.5 %, and 24.4 % (positive group: 30.6 %), respectively. Molecular docking analysis and protein–protein interaction (PPI) network revealed that compounds 2, 6, and 7 can exert neuroprotective effects through the regulation of growth factor receptor-bound protein 2 (GRB2). The discovery was beneficial to the high-value utilization of SCSL and the development of natural neuroprotective drugs.

Combination therapies may increase the antitumor effects and reduce the adverse effects for the treatment of hepatocellular carcinoma. In this study, we determined the effects of 5-fluorouracil alone or in combination with wogonin in vitro and in vivo, and we investigated the possible mechanisms. The combination of these 2 drugs led to a decrease in survival and a significant synergistic inhibitory effect on high COX-2 expression in SMMC-7721 hepatocellular carcinoma (HCC) cells. Furthermore, the results show that this combination inhibits COX-2 expression and increases sensitivity to chemotherapeutic agents partly through regulating the PI3K/Akt signaling pathway. Moreover, the combination treatment caused a significant growth inhibition of human tumor xenografts in vivo. In conclusion, wogonin may increase the cytotoxicity of some antineoplastic agents and it can be used in combination with these agents as a novel therapeutic regimen for HCC treatment. Key words: wogonin, 5-fluorouracil, synergistic effect, COX-2, PI3K/Akt. Les therapies combinees peuvent augmenter les effets anti-tumoraux et reduire les effets secondaires des medicaments utilises dans le traitement du carcinome hepatocellulaire. Dans cette etude, nous avons determine les effets du 5-fluorouracile seul ou combine a la wogonine in vitro et in vivo, et nous avons examine les mecanismes possiblement impliques dans ces effets. La combinaison de ces deux medicaments menait a une diminution de la survie cellulaire plus importante et a un effet inhibiteur synergique significatif sur l'expression de COX-2 qui est elevee dans les cellules de carcinome hepatocellulaire (CHC) SMMC-7721. De plus, les resultats montraient que la combinaison des medicaments inhibait l'expression de COX-2 et augmentait la sensibilite des cellules aux agents chimiotherapeutiques, partiellement par la regulation de la voie de signalisation de PI3K/Akt. En outre, le traitement combine resultait en une inhibition de la croissance de xenogreffes de tumeur in vivo, et ce, de maniere significative. En conclusion, la wogonine peut augmenter la cytotoxicite de certains agents anti-neoplasiques et elle peut etre utilisee en combinaison avec ces agents dans le cadre d'un nouveau protocole therapeutique de traitement du CHC. [Traduit par la Redaction] Mots-cles: wogonine, 5-fluorouracile, effet synergique, COX-2, PI3K/Akt., Introduction Hepatocellular carcinoma (HCC) ranks fifth among the most prevalent cancers in the world, and it is the third leading cause of cancer-related mortality (Livraghi et al. 2011; Yeh et [...]

5-Fluorouracil (5-FU) is a principal drug for the treatment of colorectal cancer. Due to its low response and high toxicity, synergistic effects of 5-FU in combination with other drugs have been widely researched. This study investigated whether oroxylin A improved the sensitivity of HT-29 human colon cancer cells to 5-FU. A correlation between COX-2 inhibition by oroxylin A and a synergistic effect of 5-FU on the growth of HT-29 cells was observed, and a COX-2 pathway for this effect was recognized; oroxylin A evidently elevated the level of reactive oxygen species in HT-29 cells, which subsequently inhibited COX-2 expression and enhanced the susceptibility of HT-29 cells to 5-FU. Likely also related to COX-2 inhibition, oroxylin A decreased [PGE.sub.2] levels in HT-29 cells. The synergistic effect of 5-FU induced by oroxylin A was also found in the suppression of Bcl-2 and in the activation of P53, Bax, PARP, and procaspase-3 proteins in HT-29 cells. Ultimately, a combination of 5-FU with oroxylin A significantly reduced the growth of HT-29 tumors in nude mice compared with treatment with 5-FU or oroxylin A alone. In conclusion, a combination of 5-FU and oroxylin A has a significant synergistic effect in the inhibition of HT-29 cell proliferation in vitro and controls HT-29 tumor growth in vivo. This synergistic effect may be mainly related to COX-2 inhibition by oroxylin A in HT-29 cells. Key words: 5-fluorouracil, oroxylin A, colorectal cancer cells, cyclooxygenase-2, synergistic effect. Le 5-FU est le principal medicament utilise dans le traitement du cancer colorectal. A cause d'une reponse faible et de sa haute toxicite, des effets synergiques d'un traitement au 5-FU combine a d'autres medicaments ont ete largement recherches. Cette etude visait a determiner si un traitement a l'oroxyline A ameliorait la sensibilite des cellules de cancer du colon HT-29 au 5-FU. Une correlation entre l'inhibition de COX-2 par l'oroxyline A et son effet synergique avec le 5-FU sur la croissance des cellules HT-29 a ete observee, et l'implication d'une voie impliquant COX-2 a ete mise en evidence : l'oroxyline A augmentait de maniere evidente les niveaux d'ERO dans les cellules HT-29, ce qui inhibait subsequemment l'expression de COX-2, et ce faisant, augmentait la sensibilite des cellules HT-29 au 5-FU. En lien aussi avec l'inhibition de COX-2, l' oroxyline A diminuait les niveaux de [PGE.sub.2] des cellules HT-29. L' effet synergique de l'oroxyline A sur le 5-FU a aussi ete demontre sur la suppression de Bcl-2 et l'activation de P53, Bax, la PARP, et la pro-caspase 3 chez les HT- 29. Finalement, la combinaison de 5-FU et d'oroxyline A reduisait significativement la croissance tumorale des HT-29 chez les souris nues, comparativement a un traitement au 5-FU ou a l'oroxyline A seuls. En conclusion, une combinaison de 5-FU et d'oroxyline A exerce un effet synergique significatif sur l'inhibition de la proliferation des cellules HT-29 in vitro et sur la croissance tumorale des HT-29 in vivo. Cet effet synergique peut etre principalement relie a l' inhibition de COX-2 par l'oroxyline A chez les cellules HT-29. Mots-cles : 5-fluorouracile, oroxyline A, cellules de cancer colorectal, cyclooxygenase-2, effet synergique. [Traduit par la Redaction], Introduction Colorectal cancer (CRC) has been estimated to be the third most common cause of cancer-related deaths in many countries. In the USA, CRC is the third most common cause [...]

Wogonin, a naturally occurring flavonoid, has been shown to have tumor therapeutic potential both in vitro and in vivo. To better understand its anticancer mechanism, we examined the effect of wogonin on human cervical carcinoma HeLa cells. In this study, we observed that [G.sub.1] phase arrest was involved in wogonin-induced growth inhibition in HeLa cells. Over a 24 h exposure of HeLa cells to 90 μmol * [L.sup.-1] wogonin, the promoters of [G.sub.1]-S transition, including cyclin D1/ Cdk4 and pRb, decreased within 12 h and E2F-1 depleted in the nucleus at the same time. As the [G.sub.1] phase arrest developed, p53 and the Cdk inhibitor [p21.sup.Cip1] elevated both at protein and mRNA levels. Furthermore, the up-regulation of [p21.sup.Cip1] induced by wogonin was dramatically inhibited by siRNA-mediated p53 gene silencing. Collectively, our data suggested that wogonin induced [G.sub.1] phase arrest in HeLa cells by modulating several key [G.sub.1] regulatory proteins, such as Cdk4 and cyclin D1, as well as up-regulation of a p53-midiated [p21.sup.Cip1] expression. This mechanism of wogonin may play an important role in the killing of cancerous cells and offer a potential mechanism for its anticancer action in vivo. Key words: wogonin, cell cycle, human cervical carcinoma, [p21.sup.Cip1]. La wogonine, un flavonoide naturel, a demontre un potentiel therapeutique anti-tumoral in vitro et in vivo. Dans cette etude, nous avons observe un arret de la phase [G.sub.1] chez les cellules HeLa traitees a la wogonine. Pendant une exposition de 24 h des cellules HeLa a la wogonine, les facteurs promoteurs de la transition [G.sub.1]-S, notamment la cycline D1/Cdk4 et pRb, diminuaient en moins de 12 h et la quantite de E2F-1 nucleaire diminuait en meme temps. Au fur et a mesure de la progression de l'arret en phase [G.sub.1], les quantites de p53 et de l'inhibiteur de Cdk [p21.sup.Cip1] augmentaient, tant au niveau des ARNm que des proteines. De plus, l'augmentation de l'expression de [p21.sup.Cip1] etait fortement inhibee par le silencage du gene p53 realise par un siARN. En somme, nos resultats suggerent que la wogonine a induit un arret en phase [G.sub.1] chez les cellules HeLa en modulant plusieurs proteines regulatrices cles de la phase [G.sub.1], notamment Cdk4 et la cycline D1, ainsi qu'en augmentant l'expression de [p21.sup.Cip1] dependante de p53. Mots-cles : wogonine, cycle cellulaire, carcinome de col uterin humain, Cdk4, cycline D1, [p21.sup.Cip1]. [Traduit par la Redaction], Introduction Wogonin (5,7-dihydroxy-8-methoxyflavone), an active monoflavonoid isolated from Scutellaria baicalensis Radix, is a traditional Chinese herbal medicine widely used in the treatment of inflammatory diseases (Lee et al. 2006). It [...]