The advancements and prospective developments in anti-tumor targeted therapy.

Cancer poses a major threat to human health worldwide. The development of anti-tumor materials provides new modalities for cancer diagnosis and treatment. In this review, we comprehensively summarize the research progress and clinical applications of anti-tumor materials. First, we introduce the etiology and pathogenesis of cancer, and the significance and challenges of anti-tumor materials research. Then, we classify anti-tumor materials and discuss their mechanisms of action. After that, we elaborate the research advances and clinical applications of anti-tumor materials, including those targeting tumor cells and therapeutic instruments. Finally, we discuss the future perspectives and challenges in the field of anti-tumor materials. This review aims to provide an overview of the current status of anti-tumor materials research and application, and to offer insights into future directions in this rapidly evolving field, which holds promise for more precise, efficient and customized treatment of cancer.

Discovery of dibenzylbutane lignan LCA derivatives as potent anti-inflammatory agents.

Inflammation is the body's response to defence against infection or injury, and is associated with the progression of many diseases, such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). LCA, a dibenzylbutane lignan extracted from the roots of traditional medicinal plant Litsea cubeba (Lour.) Pers., has demonstrated promising anti-inflammatory activity. In this study, a series of novel LCA derivatives were designed, synthesized, and evaluated for anti-inflammatory activity. Lipopolysaccharide (LPS)-induced RAW 264.7 cell model experiments showed that compound 10h (at 20 µM of concentration) had the strongest inhibitory effect on NO release, and inhibited the secretion and gene expression levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in vitro. In addition, western blot, immunofluorescence, and molecular docking showed that the anti-inflammatory mechanism of compound 10h may be related to the nuclear factor (NF)-κB signalling pathway. In vivo studies based on a carrageenan-induced mouse paw edema model have shown significant anti-inflammatory activity of compound 10h at 20 mg kg-1. Preliminary in vitro and in vivo studies indicate that compound 10h has the potential to be developed as a novel anti-inflammatory agent.

Research Advances in Clinical Applications, Anticancer Mechanism, Total Chemical Synthesis, Semi-Synthesis and Biosynthesis of Paclitaxel.

Paclitaxel, a natural secondary metabolite isolated and purified from the bark of the Taxus tree, is considered one of the most successful natural anticancer drugs due to its low toxicity, high potency and broad-spectrum anticancer activity. Taxus trees are scarce and slow-growing, and with extremely low paclitaxel content, the contradiction between supply and demand in the market is becoming more and more intense. Therefore, researchers have tried to obtain paclitaxel by various methods such as chemical synthesis, artificial culture, microbial fermentation and tissue cell culture to meet the clinical demand for this drug. This paper provides a comprehensive overview of paclitaxel extraction, combination therapy, total synthesis, semi-synthesis and biosynthesis in recent years and provides an outlook, aiming to provide a theoretical basis and reference for further research on the production and application of paclitaxel in the future.

Preparative separation of iridoid glucosides and crocins from Gardeniae Fructus using sequential macroporous resin column chromatography and evaluation of their anti-inflammatory and antioxidant activities.

Iridoid glycosides (geniposide (GP), genipin-1-gentiobioside (GB), etc.) and crocins (crocin Ⅰ (CR1), crocin Ⅱ(CR2), etc.) are two main bioactive components in Gardeniae Fructus (GF), which is a famous traditional Chinese medicine. Iridoid glycosides exhibit many activities and are used to manufacture gardenia blue pigment for the food industry. Crocins are rare natural water-soluble carotenoids that are often used as food colorants. A sequential macroporous resin column chromatography technology composed of HC-500B and HC-900B resins was developed to selectively separate iridoid glucosides and crocins from GF. The adsorption of GP on HC-900B resin was an exothermic process. The adsorption of CR1 on HC-500B resin was an endothermic process. The two kinds of components were completely separated by a sequential resin column. GB and GP were mainly found in product 1 (P1) with purities of 11.38% and 46.83%, respectively, while CR1 and CR2 were mainly found in product 2 (P2) with purities of 12.32% and 1.40%, respectively. The recovery yields of all the compounds were more than 80%. The above results showed that sequential resin column chromatography technology achieved high selectivity and recovery yields. GF extract, P1 and P2 could significantly inhibit the secretion of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 cells, indicating that iridoid glycosides and crocins provide a greater contribution to the anti-inflammatory activity of GF. At the same time, compared to the GF extract and P1, P2 exhibited stronger scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, indicating that crocins may provide a significant contribution to the antioxidant activity of GF.

Synthesis and in vitro Anti-proliferative Activities on LNCaP, LS180 and MKN45 of Novel 20(R)-Panaxadiol Derivatives.

BACKGROUND: 20(R)-PD, a tetracyclic triterpenoid, is a non-natural saponin present in the form of protopanaxadiol. Because of its essential biological activities, especially anti-tumor activity, structural modification of 20(R)-PD and the development of innovative and novel 20(R)-PD derivatives with better anti-tumor activity are increasingly relevant. AIMS: 20(R)-Panaxadiol (20(R)-PD) can inhibit tumor proliferation. Three series of novel 20(R-PD derivatives were synthesized by modifying the A-ring. OBJECTIVE: The objective of this work was to synthesize and evaluate the in vitro anti-proliferative activities of 20(R)- PD derivatives in LNCaP, LS180, and MKN45 cancer cells. Structural modifications were performed at the C-3 position and A-ring. METHODS: The in vitro anti-proliferative activities of novel derivatives in LNCaP, LS180, and MKN45 cells were evaluated by the MTT assay. The effects of compounds 5 and C9 on apoptosis were determined by flow cytometry. RESULTS: Compounds 5, B2, C2, C4, C7, C8, C9, C10, and C11 exhibited good anti-proliferative activities in LNCaP, LS180, and MKN45 cells in vitro. The best anti-proliferative activity was observed for the C-series derivatives with the introduction of amino acids at the C-3 position. C9 exhibited good potent activity with an IC50 of 2.89 µM. CONCLUSION: Compound C9 is a potential candidate with potent anti-proliferative activity.

Dioscorea spp.: Bioactive Compounds and Potential for the Treatment of Inflammatory and Metabolic Diseases.

Dioscorea spp. belongs to the Dioscoreaceae family, known as "yams", and contains approximately 600 species with a wide distribution. It is a major food source for millions of people in tropical and subtropical regions. Dioscorea has great medicinal and therapeutic capabilities and is a potential source of bioactive substances for the prevention and treatment of many diseases. In recent years, increasing attention has been paid to the phytochemicals of Dioscorea, such as steroidal saponins, polyphenols, allantoin, and, in particular, polysaccharides and diosgenin. These bioactive compounds possess anti-inflammatory activity and are protective against a variety of inflammatory diseases, such as enteritis, arthritis, dermatitis, acute pancreatitis, and neuroinflammation. In addition, they play an important role in the prevention and treatment of metabolic diseases, including obesity, dyslipidemia, diabetes, and non-alcoholic fatty liver disease. Their mechanisms of action are related to the modulation of a number of key signaling pathways and molecular targets. This review mainly summarizes recent studies on the bioactive compounds of Dioscorea and its treatment of inflammatory and metabolic diseases, and highlights the underlying molecular mechanisms. In conclusion, Dioscorea is a promising source of bioactive components and has the potential to develop novel natural bioactive compounds for the prevention and treatment of inflammatory and metabolic diseases.

Current Perspectives on Paclitaxel: Focus on Its Production, Delivery and Combination Therapy.

Paclitaxel is an anticancer drug first isolated from the bark of the Pacific yew tree. It has been widely used for the treatment of ovarian, breast, uterine and other cancers because of its low toxicity, high efficiency and broad-spectrum anticancer activity, and it is considered to be one of the most successful natural anticancer drugs available. Paclitaxel is a microtubule-targeting drug whose main molecular mechanism is to disrupt microtubule dynamics and induce mitotic arrest and cell death. Despite the many clinical successes of paclitaxel, the extraction of natural paclitaxel from Taxus species has proven to be environmentally unsustainable and economically unviable. As a result, researchers are constantly working to find innovative ways to meet society's need for this drug. Currently, many methods, including artificial cultivation, microbial fermentation, chemical synthesis, and tissue and cell culture, have been explored and developed to obtain paclitaxel. In addition, the poor water solubility of paclitaxel has led to significant limitations in its clinical application. Conventional paclitaxel formulations use Cremophor EL and ethanol to dissolve paclitaxel, which can lead to serious side effects. In recent decades, a series of new nanotechnology-based paclitaxel dosage forms have been developed, including albumin-bound paclitaxel, polymeric micellar paclitaxel, polymer-paclitaxel couples, and liposome-encapsulated paclitaxel. These nanoformulations can significantly reduce the toxicity of paclitaxel and greatly improve its anti-tumor efficiency. This paper reviews the development of the production, dosage form and combination therapy of paclitaxel in recent years and presents an outlook, with the aim of providing a theoretical basis and reference for further research on the production and application of paclitaxel in the future.

Anti-inflammatory activity of fluorine-substituted benzo[h]quinazoline-2-amine derivatives as NF-κB inhibitors.

Excessive inflammation can cause loss of tissue or organ function, leading to a number of chronic diseases and sometimes even death. Traditional treatment strategies for inflammation have mainly involved steroidal and non-steroidal anti-inflammatory drugs, but both have increasingly prominent side effects. Nuclear factor kappa B (NF-κB) inhibitors with anti-inflammatory properties and low toxicity are a new therapeutic strategy for the treatment of inflammatory diseases. To obtain novel NF-κB inhibitors, a series of 3,4-dihydronaphthalen-1(2H)-one derivatives (DHNs 6a-s), 1,4,5,6-tetrahydrobenzo[h]quinazolin-2-amine derivatives (BQAs 7a-c) and 5,6-dihydrobenzo[h]quinazolin-2-amine derivatives (BQAs 8a-p) were designed and synthesized, and characterized by NMR and HRMS. By evaluating toxicity and anti-inflammatory properties, fluorine-substituted 8c showed more potential anti-inflammatory activity and lower toxicity. 8c significantly reduced the phosphorylation of IκBα and p65, thereby inhibiting the NF-κB signaling pathway. In addition, 8c markedly decreased reactive oxygen species (ROS) production and downregulated the expression of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and cysteine aspartate protein hydrolase-1 (caspase-1). Therefore, compound 8c is expected to be a candidate compound for NF-κB inhibition and deserves further research and development.

Stereoscopic Differences in the Identification, Bioactivity, and Metabolism of C-20 and C-24 Epimeric Ginseng Saponins.

Ginseng, the roots and/or rhizomes of Panax spp.(Araliaceae), has been used as a popular herbal medicine in East Asia for at least two millennia. As a functional food and healthenhancing supplement, ginseng has been shown to have a wide range of pharmacological effects on cognition and blood circulation as well as antioxidant, antitumor, and anti-fatigue effects. The main active properties of ginseng are considered to be the triterpene saponins, often referred to as ginsenosides, which are the basis for their wide-ranging pharmacological effects. Four of these glycosides, including protopanaxadiol, protopanaxatriol, ocotillol, and oleanolic acid, are the most common saponins found in ginseng. Compared to other ginsenosides, the C-20 chimeric ginsenosides, including Rg3, Rh2, Rg2, Rh1, PF11, C-20, and C-24, as well as epimeric ocotillol-type saponins and their derivatives exhibit significant, steric differences in biological activity and metabolism. 20(R)-ginseng saponins, one class of important rare ginsenosides, have antitumor, antioxidative, antifatigue, neuroprotective and osteoclastogenesis inhibitory effects. However, 20(R)- ginsenosides are rare in natural products and are usually prepared from 20(S)-isomers through chemical differential isomerization and microbial transformation. The C20 configuration of 20(R)-ginseng saponins is usually determined by 13C NMR and X-ray single-crystal diffraction. There are regular differences in the chemical shift values of some of the carbons of the 20(S)- and 20(R)-epimers, including C-17, C-21, and C-22. Owing to their chemical structure and pharmacological and stereoselective properties, 20(R)-ginseng saponins have attracted a great deal of attention in recent years. Herein, the stereoscopic differences in the identification, bioactivity, and metabolism of C-20 and C-24 epimeric ginseng saponins are summarized.

Phytochemistry, health benefits, and food applications of sea buckthorn (Hippophae rhamnoides L.): A comprehensive review.

Sea buckthorn (Hippophae rhamnoides L.), an ancient miraculous plant, is of great interest because of its tenacity, richness in nutritional active substances, and biological activity. Sea buckthorn is a deciduous shrub or tree of the genus Hippophae in the family Elaeagnaceae. It is a pioneer tree species for soil improvement, wind and sand control, and soil and water conservation. Sea buckthorn contains many nutritional active components, such as vitamins, carotenoids, polyphenols, fatty acids, and phytosterols. Moreover, sea buckthorn has many health benefits, such as antioxidant, anticancer, anti-hyperlipidemic, anti-obesity, anti-inflammatory, antimicrobial, antiviral, dermatological, neuroprotective, and hepatoprotective activities. Sea buckthorn not only has great medicinal and therapeutic potential, but also is a promising economic plant. The potential of sea buckthorn in the human food industry has attracted the research interest of researchers and producers. The present review mainly summarizes the phytochemistry, nutrients, health benefits, and food applications of sea buckthorn. Overall, sea buckthorn is a dietary source of bioactive ingredients with the potential to be developed into functional foods or dietary supplements for the prevention and treatment of certain chronic diseases, which deserves further research.

Sesame (Sesamum indicum L.): A Comprehensive Review of Nutritional Value, Phytochemical Composition, Health Benefits, Development of Food, and Industrial Applications.

Sesame (Sesamum indicum L.), of the Pedaliaceae family, is one of the first oil crops used in humans. It is widely grown and has a mellow flavor and high nutritional value, making it very popular in the diet. Sesame seeds are rich in protein and lipids and have many health benefits. A number of in vitro and in vivo studies and clinical trials have found sesame seeds to be rich in lignan-like active ingredients. They have antioxidant, cholesterol reduction, blood lipid regulation, liver and kidney protection, cardiovascular system protection, anti-inflammatory, anti-tumor, and other effects, which have great benefits to human health. In addition, the aqueous extract of sesame has been shown to be safe for animals. As an important medicinal and edible homologous food, sesame is used in various aspects of daily life such as food, feed, and cosmetics. The health food applications of sesame are increasing. This paper reviews the progress of research on the nutritional value, chemical composition, pharmacological effects, and processing uses of sesame to support the further development of more functionalities of sesame.

Celastrol inhibits rheumatoid arthritis by inducing autophagy via inhibition of the PI3K/AKT/mTOR signaling pathway.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder of the synovial joints. Celastrol (Cel) is a quinone-methylated triterpenoid extracted from Tripterygium wilfordii Hook F (TwHF) that has been proven to be effective in treating RA. However, the underlying molecular mechanism of celastrol in the treatment of RA remains unknown. This study explored the protective effect of celastrol against RA and the specific mechanisms of celastrol in vitro and in vivo. METHODS: A chicken type II collagen (CII)-induced arthritis (CIA) mouse model was used to explore the anti-arthritic effects of celastrol, and paw swelling degree, the poly-arthritis index score and serum cytokine levels were determined. Pathological morphology was observed using hematoxylin and eosin (H&E) staining. The influences of celastrol on the proliferation of tumor necrosis factor-α (TNF-α)-induced fibroblast-like synoviocytes (FLSs) were tested by Cell Counting Kit-8 (CCK-8) assays and5-ethynyl-2'-deoxyuridine (EdU) staining assays. The level of autophagy was detected by transmission electron microscopy (TEM). Furthermore, the PI3K/AKT/mTOR pathway and the status of autophagy in the CIA model and FLSs were also detected by western blot and immunofluorescence staining. RESULTS: The results showed that celastrol decreased arthritis severity and inhibited TNF-α-induced FLSs proliferation. Additionally, celastrol decreased the secretion of pro-inflammatory cytokines. Moreover, celastrol increased autophagosome levels and LC3B protein expression in TNF-α-treated FLSs. Furthermore, celastrol increased the protein expression of LC3-II and Beclin-1 and decreased the phosphorylation degree of mTOR and AKT. CONCLUSION: In conclusion, our findings confirmed that celastrol ameliorates RA via the up-regulation of autophagy by inhibiting the PI3K/AKT/mTOR axis.

Platycodon grandiflorum (Jacq.) A. DC.: A review of phytochemistry, pharmacology, toxicology and traditional use.

BACKGROUND: The traditional Chinese medicine Platycodon grandiflorum (Jacq.) A. DC. (PG, balloon flower) has medicinal and culinary value. It consists of a variety of chemical components including triterpenoid saponins, polysaccharides, flavonoids, polyphenols, polyethylene glycols, volatile oils and mineral components, which have medicinal and edible value. PURPOSE: The ultimate goal of this review is to summarize the phytochemistry, pharmacological activities, safety and uses of PG in local and traditional medicine. METHODS: A comprehensive search of published literature up to March 2022 was conducted using the PubMed, China Knowledge Network and Web of Science databases to identify original research related to PG, its active ingredients and pharmacological activities. RESULTS: Triterpene saponins are the primary bioactive compounds of PG. To date, 76 triterpene saponin compounds have been isolated and identified from PG. In addition, there are other biological components, such as flavonoids, polyacetylene and phenolic acids. These extracts possess antitussive, immunostimulatory, anti-inflammatory, antioxidant, antitumor, antiobesity, antidepressant, and cardiovascular system activities. The mechanisms of expression of these pharmacological effects include inhibition of the expression of proteins such as MDM and p53, inhibition of the activation of enzymes, such as AKT, the secretion of inflammatory factors, such as IFN-γ, TNF-α, IL-2 and IL-1ß, and activation of the AMPK pathway. CONCLUSION: This review summarizes the chemical composition, pharmacological activities, molecular mechanism, toxicity and uses of PG in local and traditional medicine over the last 12 years. PG contains a wide range of chemical components, among which triterpene saponins, especially platycoside D (PD), play a strong role in pharmacological activity, representing a natural phytomedicine with low toxicity that has applications in food, animal feed and cosmetics. Therefore, PG has value for exploitation and is an excellent choice for treating various diseases.

Food Applications and Potential Health Benefits of Hawthorn.

Hawthorn (Crataegus) is a plant of the Rosaceae family and is widely grown throughout the world as one of the medicinal and edible plants, known as the "nutritious fruit" due to its richness in bioactive substances. Preparations derived from it are used in the formulation of dietary supplements, functional foods, and pharmaceutical products. Rich in amino acids, minerals, pectin, vitamin C, chlorogenic acid, epicatechol, and choline, hawthorn has a high therapeutic and health value. Many studies have shown that hawthorn has antioxidant, anti-inflammatory, anticancer, anti-cardiovascular disease, and digestive enhancing properties. This is related to its bioactive components such as polyphenols (chlorogenic acid, proanthocyanidin B2, epicatechin), flavonoids (proanthocyanidins, mucoxanthin, quercetin, rutin), and pentacyclic triterpenoids (ursolic acid, hawthornic acid, oleanolic acid), which are also its main chemical constituents. This paper briefly reviews the chemical composition, nutritional value, food applications, and the important biological and pharmacological activities of hawthorn. This will contribute to the development of functional foods or nutraceuticals from hawthorn.

Structure elucidation and antitumor activity of a water soluble polysaccharide from Hemicentrotus pulcherrimus.

Sea urchin nowadays serves as a delicacy around the world, and its gonads accumulate abundant polysaccharides before gametogenesis. However, the structure and bioactivity of these polysaccharides remain less well understood. Herein, a water soluble polysaccharide (HPP-1S) with a molecular weight of 2.996 × 107 Da was purified from the gonads of Hemicentrotus pulcherrimus. Chemical, spectroscopic and oligosaccharide sequencing analyses revealed that HPP-1S was a highly homogeneous polysaccharide featuring a linear backbone of 1,4-linked α-d-glucose with 1,6-α-d-glucose and 1,6-α-D-glucuronic acid side chains grafted on the backbone in an alternating pattern. In vitro, HPP-1S can arrest the cell cycle at G2/M and sub-G1 phases, and induce apoptosis in Hela cells potentially by increasing expression ratio of Bax/Bcl-2. In vivo, HPP-1S exhibited obvious antitumor efficacy in Hela xenograft-bearing nude mice with low toxicity. These findings indicated that HPP-1S might serve as a potential low toxic antitumor agent.

Synthesis, biological evaluation and molecular docking studies of novel diosgenin derivatives as anti-inflammatory agents.

Thirty-two novel DG F-spiroacetal ring-opening derivatives, including 24 acetylated derivatives and 8 nitrogenous derivatives, were designed and synthesized from diosgenin (DG). The cytotoxicity of the novel derivatives was evaluated by MTT assay, except for compounds 4a, 4e, 4i, 4 l, 5a and 5 h, which were potentially cytotoxic to RAW264.7 cells, all the other derivatives had no significant cytotoxicity. The NO release inhibitory activities of novel derivatives were screened by Griess method. The results showed that the anti-inflammatory activity of the DG acetylated derivatives was stronger than the nitrogenous derivatives, and 4a-4 m containing acetyl groups at the 3-position may have better anti-inflammatory effects than 5a-5 k containing free hydroxyl groups. In ELISA assay, compound 4 m exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by LPS with IC50 values 0.449 ± 0.050 µM. The results of docking experiments showed that 4 m has a good affinity for p65 protein.

Design and synthesis of novel aza-ursolic acid derivatives: in vitro cytotoxicity and nitric oxide release inhibitory activity.

Aim: Inducible nitric oxide synthase (iNOS) is a validated target for anti-inflammatory treatment. Based on the authors' previous work, novel aza-ursolic acid derivatives were designed and synthesized and their inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) release from RAW264.7 cells was evaluated. Materials & results: 16 novel derivatives were screened for their in vitro inhibitory activity against NO release using Griess assays and the cytotoxicity was evaluated using MTT assays. The presence of furoxan joined to the A-ring of ursolic acid and N-methylpiperazine groups in the lead compound was identified for anti-inflammatory activity, and compound 21b showed 94.96% inhibition of NO release at 100 µM with an IC50 value of 8.58 µM. Conclusion: Compound 21b has potential anti-inflammatory activity with low cytotoxicity that warrants further preclinical study and evaluation.

Phytochemistry, bioactivities and future prospects of mulberry leaves: A review.

Mulberry leaves (MLs) have been used traditionally to raise silkworms and as herbs and herbal drinks. In vitro and in vivo studies as well as some clinical trials provide some evidence of health benefits, mostly for ML extracts. ML extracts showed antioxidant, hypoglycemic, anticholesterol (affecting lipid metabolism), antiobesity, anti-inflammatory, anticancer activities, and so on. These might be linked to strong antioxidant activities, inhibition of α-glucosidase and α-amylase, reduction of foam cell formation, inhibition of fat formation, decrease of NF-κB activity, and the promotion or induction of apoptosis. Phenolic constituents, especially flavonoids, phenolic acids and alkaloids, are likely to contribute to the reported effects. The phytochemistry and pharmacology of MLs confer the traditional and current uses as medicine, food, fodder, and cosmetics. This paper reviews the economic value, chemical composition and pharmacology of MLs to provide a reference for the development and utilization of MLs.

Discovery of anti-hepatoma agents from 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidine by inhibiting PI3K/AKT/NF-κB pathway activation.

In order to obtain new anti-hepatoma drugs with low toxicity, some 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidines (PPMs, 4a-t) were synthesized in this study. Many of them showed significant anti-hepatoma effects against HCC cells and low toxicity toward HHL-5 cells. Combined with their anti-hepatoma activity and toxicity, 4-CF3-substituted 4k was selected as an effective lead compound. Preliminary mechanistic studies revealed that 4k could up-regulate the expression levels of Bax and caspase-3 proteins, down-regulate the expression levels of Bcl-2 protein, promote significant apoptosis of HepG2, and block cells in G2-M phase to prevent cells from completing mitosis. Also, 4k could significantly inhibit the activation of PI3K/AKT/NF-κB pathway by blocking the phosphorylation of PI3K, AKT, NF-κB/p65 and IFN-γ-induced nuclear transport. Docking analysis showed that 4k could reasonably bind to the active sites of Bcl-2, NF-κB/p65, PI3K and AKT. This result suggested that 4k could be used as a new type of NF-κB inhibitor, which provides a scientific basis for further research into the treatment of hepatoma.

Separation of three chromones from Saposhnikovia divaricata using macroporous resins followed by preparative high-performance liquid chromatography.

Prim-O-glucosylcimifugin, cimifugin, and 5-O-methylvisamminoside are three major chromone derivatives of Saposhnikovia divaricata that have many pharmacological activities, such as anti-inflammatory and antitumor activities. In the present work, an effective method for the simultaneous separation of prim-O-glucosylcimifugin, cimifugin, and 5-O-methylvisamminoside with high purities was established using HPD-300 resin coupled with preparative high-performance liquid chromatography. The adsorption kinetics curves of the three compounds on the HPD-300 resin were studied and found to fit well according to the pseudo-second-order equation. The adsorption isotherm results indicated that the adsorption process of the three compounds was exothermic. After a one-run treatment with the resin, the contents of prim-O-glucosylcimifugin, cimifugin, and 5-O-methylvisamminoside increased from 0.29, 0.06, and 0.37% to 13.07, 2.83, and 16.91% with recovery yields of 76.38, 78.25, and 76.73%, respectively. Finally, the purities of the three compounds were found to reach more than 95% after further separation using preparative high-performance liquid chromatography. The method developed in this study was effective and could simultaneously separate three chromones from Saposhnikovia divaricate. The experimental results also showed that the HPD-300 resin is suitable for the separation of chromone derivatives.