A New Calculation Model for Calcium Requirements After Parathyroidectomy in Patients With Secondary Hyperparathyroidism.

OBJECTIVES: We aimed to develop a new calculation model for calcium requirements in dialysis patients following parathyroidectomy. METHODS: A total of 98 patients with secondary hyperparathyroidism receiving parathyroidectomy from January 2014 to January 2022 were enrolled in this study. Among these patients, 78 were randomly selected for construction of the calcium requirement calculation model, and the remaining 20 patients were selected for model validation. The calcium requirement model estimated the total calcium supplementation for 1 week after surgery using variables with significant relationships in the derivation group by stepwise multiple linear regression analysis. Bias, precision, and accuracy were measured in the validation group to determine the performance of the model. RESULTS: The model was as follows: calcium requirement for 1 week after surgery=33.798-8.929×immediate postoperative calcium+0.190×C-reactive protein-0.125×age+0.002×preoperative intact parathyroid hormone+0.003×preoperative alkaline phosphatase (R2=0.8). The model was successfully validated. CONCLUSION: We generated a novel model to guide calcium supplementation. This model can assist in stabilizing the serum calcium levels of patients during the early postoperative period. Furthermore, it contributes to the individualized and precise treatment of hypocalcemia in patients following parathyroidectomy.

The influence of residual pectin composition and content on nanocellulose films from ramie fibers: Micro-nano structure and physical properties.

In this study, cellulose nanofibril (CNF) films from ramie fibers were prepared with different pectin compositions and contents, and the influence of residual pectin on the overall performances of CNF films was evaluated. There was no significant effect of the residual pectin composition on the properties of obtained CNF films. However, when the content of residual pectin was increased from 0.45 % to 9.16 %, the surface area and water absorption of CNF films were increased from 0.2223 to 0.3300 m2/g, and from 93.51 % to 122.42 %, respectively. Pectin covers the CNF surface and act as a physical barrier between the cellulose fibrils; thus the nanocellulose films with high pectin content will have a loose and porous structure, resulting in a high surface area and a high water absorption. Besides, with the residual pectin content decreasing from 9.16 % to 0.45 %, the UVA light transmittance and tensile strength of CNF films were increased from 30.6 % to 59.9 %, and from 37.67 to 100.26 MPa, respectively. After removal of amorphous pectins in CNFs, the low pectin containing CNFs are able to pack more compactly to form a strong and thin film. This paper provides guidance for the preparation of CNF films with different performance requirements.

Vitamin D3 and Lactobacillus rhamnosus GG/p40 Synergize to Protect Mice From Colitis by Promoting Vitamin D Receptor Expression and Epithelial Proliferation.

BACKGROUND: While vitamin D (VitD) levels are negatively correlated with inflammatory bowel disease (IBD) activity, VitD supplementation does not reduce IBD severity. The probiotic Lactobacillus rhamnosus GG (LGG), which secretes p40, can upregulate colonic VitD receptor (VDR) expression. We therefore evaluated synergy between VitD3 and LGG/p40 in the treatment of mouse colitis. METHODS: A dextran sulfate sodium (DSS) colitis model was established in Vdr+/+ and Vdr-/- mice, and mice were treated with VitD3, LGG, or p40 alone or in combination for 7 to 14 days. Colitis severity was assessed by weight loss, disease activity index (DAI), colon length, histology, and inflammatory cytokine expression together with VDR expression, proliferation, and apoptosis. In vitro, VDR expression and cell viability were assessed in HCT116 cells after stimulation with p40. RESULTS: Total and nuclear VDR protein expression were lower in DSS-treated Vdr+/+ mice compared with control mice (P < .05). Compared with the DSS group, VitD3 + LGG alleviated colitis as assessed by significantly improved DAI and histological scores, increased colon length, decreased colonic Tnf, and increased Il10 expression together with increased colonic VDR gene and protein expression and increased Ki-67 proliferation index (P < .05). In Vdr-/- mice, VitD3 + LGG had no effect on DSS colitis. In Vdr+/+ mice, VitD3 + p40 also reduced colitis severity according to clinicopathological and immunological metrics and increased VDR expression and epithelial proliferation (P < .05). In HCT116 cells, p40 stimulation increased VDR protein expression and viability (P < .05). CONCLUSIONS: VitD3 and LGG/p40 synergistically improve the severity of colitis by increasing colonic VDR expression and promoting colonic epithelial proliferation.

There is increasing evidence that vitamin D and its associated pathways may be a helpful adjunct to inflammatory bowel disease therapies. This experimental study shows that vitamin D may synergize with the probiotic Lactobacillus rhamnosus GG for enhanced therapeutic effect.

Effects of residual pectin composition and content on the properties of cellulose nanofibrils from ramie fibers.

In this study, a series of pretreatment methods (pectin extraction) were employed to prepare cellulose nanofibrils (CNFs) with different pectin composition and contents from ramie fibers. The comprehensive effects of residual pectin on the final properties of CNFs were investigated. The residual pectin did not have a significant effect on the size distribution of the obtained CNFs. While the presence of pectin led to higher zeta potential value, improved dispersion stability and enhanced storage modulus of the CNF dispersion, with the sodium carbonate extraction method showing the greatest impact. The possible mechanism for enhanced dispersion stability of CNFs is the formation of self-assembled hierarchical pectin-hemicellulose/lignin-cellulose nanostructures, offering abundant electrostatic repulsion and steric hindrance between the nanoparticles. This work provides guidelines for the tailored production of CNFs to meet the requirements for different applications.

Anti-oral Cancer Biological Activity Evaluation and Chloroplast Genome Analyses of Populus euphratica.

In this research, the anti-cancer activity of the Populus euphratica extract was evaluated with Cell Counting Kit-8 (CCK-8) assay. The inhibitory activity of the Populus euphratica extract on the activation levels of VEGF signaling pathway in the cancer cells was measured with real time RT-PCR. Next, the high-throughput Illumina pair-end sequencing was performed to detect the chloroplast (cp) genome of Populus euphratica for genome evolution assessment. The CCK-8 results indicated that the extract of Populus euphratica exhibited the significantly suppression effect on the viability of the cancer cells, and the data of the real time RT-PCR showed the activation levels of VEGF signaling pathway in the cancer cells was also reduced obviously by the Populus euphratica extract. The circular cp genome of the Populus euphratica is 157,806 bp, encoding 131 genes, containing 8 Ribosomal RNA genes (rRNAs), 37 Transfer RNA genes (tRNAs) and 86 Protein coding genes (PCGs). And the results of the phylogenetic analysis indicated that the Populus euphratica. Furthermore, phylogenetic analysis revealed that Populus euphratica has the closest relationship with Populus pruinosa. In addition to Populus pruinosa, Populus ilicifolia also has closely relationship with Populus euphratica. These three species could be clustered on the same clade.

Screening potential antagonists of epidermal growth factor receptor from Marsdenia tenacissima via cell membrane chromatography model assisted by HPLC-ESI-IT-TOF-MS.

Marsdenia tenacissima, or Tongguanteng in Chinese, is a traditional Chinese herb and has a broad application in clinical practice for its pharmacological effects of treating asthma, pneumonia, tonsillitis, pharyngitis tumors, etc. However, few studies have reported the screening of the active components of this medicine for tumor therapy. In this work, a two-dimensional analytical system was developed to screen antagonists of epidermal growth factor receptor (EGFR) from M. tenacissima. A fraction was retained on the EGFR cell membrane chromatography (CMC) column, separated and identified as tenacissoside G (TG), tenacissoside H (TH) and tenacissoside I (TI) by two-dimensional HPLC-IT-TOF-MS. Molecular docking and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay were carried out to assess the activity of TS (including TG, TH and TI). Molecular docking results showed that the binding mode of TS on EGFR is similar to that of gefitinib. The MTT assay demonstrated that gefitinib and TS (especially TI) could inhibit the growth of EGFR highly expressed cell lines in a dose-dependent manner in the range of 5-50 µmol/L. In conclusion, the two-dimensional EGFR/CMC-HPLC-IT-TOF-MS system could be a useful approach in drug discovery from traditional Chinese medicines for searching for potential antitumor candidates.

Ephrin type-B receptor 4 affinity chromatography: An effective and rapid method studying the active compounds targeting Ephrin type-B receptor 4.

Erythropoietin-producing hepatocyte B4 (EphB4) has recently been reported to be an oncogenic factor in many cancers and overexpressed in several types of tumors. Thus, EphB4 has the potential to be a therapeutic target in these malignancies. High-performance affinity chromatography has been a powerful tool to study the interaction between drugs and receptors. In this study, we constructed a novel EphB4 affinity chromatography model to investigate the active compounds which can target EphB4. More than 50 crude extracts of traditional Chinese medicine were screened by this affinity chromatography model. The active ingredients sanguinarine from celandine and macleaya cordata, and berberine from coptis chinensis and phellodendron amurense were found to selectively bind on the EphB4 affinity column. Next biological evaluatation data showed that EphB4 played a critical role in the inhibitory effect of sanguinarine and berberine on cancer cell growth. The results indicated that EphB4 affinity chromatography model constructed in this study can be used to screen the active compounds targeting EphB4 effectively and rapidly, especially in natural products.

Synergistic effect of berberine and HMQ1611 impairs cell proliferation and migration by regulating Wnt signaling pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a biologically complex disease. Combination chemotherapy is a good strategy after surgery treatment. In this study, we report that berberine combined with HMQ1611 (BCH) had a good synergistic effect on the HCC. Our findings concluded that BCH showed good inhibition on the HCC proliferation and colony formation, which attributed to cell cycle arrest by BCH at G1 phase through impairing the expression of cyclinD1, cyclinE, and cdc2 and downregulated the phosphorylation of Akt, mTOR, and ERK. Moreover, BCH negatively regulated Wnt signaling pathway by upregulating the Axin and inhibiting the nuclear translocation of ß-catenin. BCH suppressed the phosphorylation of LRP5/6, GSK3ß, the expression of Wnt5a, Frizzled8, CK1, and APC, as well as the nucleus protein included MMP2, MMP3, MMP9, and c-myc. The above data of Wnt signaling regulators contributed to inhibition by BCH on cell migration. In vivo studies, BCH significantly suppressed the growth of SMMC-7721 xenograft tumors through downregulating Ki67 and ß-catenin, as well as upregulating Axin and p-ß-catenin. In conclusion, the results revealed that BCH exhibited potential antitumor activities against human liver cancer in vitro and in vivo, and the potential mechanism underlying these activities depended on the inhibition of the Wnt/ß-catenin signaling pathway.

The mitigation effects of exogenous melatonin on replant disease in apple.

Melatonin mediates many physiological processes in plants. The problem of apple replant disease is unsolved. Our study objectives were to evaluate the regulatory effect of melatonin on plant resistance to this challenge and investigate the preliminary mechanism by which melatonin helps alleviate the effects of this disease. Two-year-old trees of "Fuji" apple (Malus domestica), grafted onto rootstock M.26, were grown in "replant" soil for 6 months in the absence or presence of a 200 µmol/L melatonin supplement. The addition of melatonin to the soil significantly increased the rates of plant growth and net photosynthesis and chlorophyll concentrations under replant conditions. This molecule elevated the levels of K in leaves and roots and enhanced the activity of soil enzymes. Such supplementation also changed the composition of the bacterial and fungal communities in the soil. We concluded that the application of melatonin to a replant soil can protect their chloroplasts from oxidative damage and release the apple root from membrane damage, and also lead to increased soil enzyme activity and soil quality while altering the composition of bacterial and fungal communities. These changes can then promote seedling growth, stimulate photosynthesis, and elevate K levels, thereby alleviating the effects of apple replant disease.

Ultrasonic Assisted Extraction of Paclitaxel from Taxus x media Using Ionic Liquids as Adjuvants: Optimization of the Process by Response Surface Methodology.

(1) Background: Ionic liquids (ILs) are considered "green" solvents and have been widely used in the extraction and separation field in recent years; (2) Methods: In this study, some common ILs and functionalized magnetic ionic liquids (MILs) were used as adjuvants for the solvent extraction of paclitaxel from Taxus x media (T. x media) using methanol solution. The extraction conditions of methanol concentration, IL type and amount, solid-liquid ratio, extraction temperature, and ultrasonic irradiation time were investigated in single factor experiments. Then, three factors of IL amount, solid-liquid ratio, and ultrasonic irradiation time were optimized by response surface methodology (RSM); (3) Results: The MIL [C4MIM]FeCl3Br was screened as the optimal adjuvant. Under the optimization conditions of 1.2% IL amount, 1:10.5 solid-liquid ratio, and 30 min ultrasonic irradiation time, the extraction yield reached 0.224 mg/g; and (4) Conclusions: Compared with the conventional solvent extraction, this ultrasonic assisted extraction (UAE) using methanol and MIL as adjuvants can significantly improve the extraction yield, reduce the use of methanol, and shorten the extraction time, which has the potentiality of being used in the extraction of some other important bioactive compounds from natural plant resources.

E-cadherin Mediates the Preventive Effect of Vitamin D3 in Colitis-associated Carcinogenesis.

Vitamin D3 is beneficial in ameliorating or preventing inflammation and carcinogenesis. Here, we evaluated if vitamin D3 has a preventive effect on colitis-associated carcinogenesis. Administration of azoxymethane (AOM), followed with dextran sulfate sodium (DSS), was used to simulate colitis-associated colon cancer in mice. The supplement of vitamin D3 at different dosages (15, 30, 60 IU·g·w), started before AOM or immediately after DSS treatment (post 60), was sustained to the end of the experiment. Dietary vitamin D3 significantly reduced the number of tumors and tumor burden in a dose-dependent manner. Of note, vitamin D3 in high doses showed significant preventive effects on carcinogenesis regardless of administration before or after AOM-DSS treatment. Cell proliferation decreased in vitamin D3 groups compared with the control group after inhibition of expression of ß-catenin and its downstream target gene cyclin D1 in the colon. In vitro, vitamin D3 reduced the transcriptional activity and nuclear level of ß-catenin, and it also increased E-cadherin expression and its binding affinity for ß-catenin. Moreover, repression of E-cadherin was rescued by supplemental vitamin D3 in mouse colons. Taken together, our results indicate that vitamin D3 effectively suppressed colonic carcinogenesis in the AOM-DSS mouse model. Our findings further suggest that upregulation of E-cadherin contributes to the preventive effect of vitamin D3 on ß-catenin activity.

Extraction of Oil from Flaxseed (Linum usitatissimum L.) Using Enzyme-Assisted Three-Phase Partitioning.

In this study, enzyme-assisted three-phase partitioning (EATPP) was used to extract oil from flaxseed. The whole procedure is composed of two parts: the enzymolysis procedure in which the flaxseed was hydrolyzed using an enzyme solution (the influencing parameters such as the type and concentration of enzyme, temperature, and pH were optimized) and three-phase partitioning (TPP), which was conducted by adding salt and t-butanol to the crude flaxseed slurry, resulting in the extraction of flaxseed oil into alcohol-rich upper phase. The concentration of t-butanol, concentration of salt, and the temperature were optimized to maximize the extraction yield. Under optimized conditions of a 49.29 % t-butanol concentration, 30.43 % ammonium sulfate concentration, and 35 °C extraction temperature, a maximum extraction yield of 71.68 % was obtained. This simple and effective EATPP can be used to achieve high extraction yields and oil quality, and thus, it is potential for large-scale oil production.

Extraction, Preconcentration and Isolation of Flavonoids from Apocynum venetum L. Leaves Using Ionic Liquid-Based Ultrasonic-Assisted Extraction Coupled with an Aqueous Biphasic System.

BACKGROUND: Ionic liquids (ILs) are considered as green solvents, and widely applied for the extraction of various compounds. METHODS: The present research focuses on the extraction of flavonoids from Apocynum venetum L. leaves by ultrasound-assisted extraction (UAE). Several major influencing factors were optimized. Then, an aqueous biphasic system (ABS) was applied for further isolation of flavonoids. RESULTS: The flavonoids were mainly distributed in the top phase, while impurities were extracted to the bottom phase. The parameters influencing the extraction, namely type and concentration of salt, temperature, and pH, were studied in detail. Under optimized conditions (72.43% IL extract, 28.57% (NH4)2SO4, 25 °C temperature, pH 4.5), the preconcentration factor and extraction efficiency were found to be 3.78% and 93.35%, respectively. CONCLUSIONS: This simple and efficient methodology is expected to see great use in the extraction and isolation of pharmaceutically active components from medicinal plant resources.

Ionic Liquid-Based Ultrasonic-Assisted Extraction of Secoisolariciresinol Diglucoside from Flaxseed (Linum usitatissimum L.) with Further Purification by an Aqueous Two-Phase System.

In this work, a two-step extraction methodology of ionic liquid-based ultrasonic-assisted extraction (IL-UAE) and ionic liquid-based aqueous two-phase system (IL-ATPS) was developed for the extraction and purification of secoisolariciresinol diglucoside (SDG) from flaxseed. In the IL-UAE step, several kinds of ILs were investigated as the extractants, to identify the IL that affords the optimum extraction yield. The extraction conditions such as IL concentration, ultrasonic irradiation time, and liquid-solid ratio were optimized using response surface methodology (RSM). In the IL-ATPS step, ATPS formed by adding kosmotropic salts to the IL extract was used for further separation and purification of SDG. The most influential parameters (type and concentration of salt, temperature, and pH) were investigated to obtain the optimum extraction efficiency. The maximum extraction efficiency was 93.35% under the optimal conditions of 45.86% (w/w) IL and 8.27% (w/w) Na2SO4 at 22 °C and pH 11.0. Thus, the combination of IL-UAE and IL-ATPS makes up a simple and effective methodology for the extraction and purification of SDG. This process is also expected to be highly useful for the extraction and purification of bioactive compounds from other important medicinal plants.

Effect of Shenkang granules on the progression of chronic renal failure in 5/6 nephrectomized rats.

Shenkang granules (SKGs) are a Chinese herbal medicinal formula, consisting of rhubarb (Rheum palmatum L.), Salvia miltiorrhiza, milkvetch root [Astragalus membranaceus (Fisch.) Bunge] and safflower (Carthamus tinctorius L.). The aim of the present study was to investigate the effect of SKG on chronic renal failure (CRF) in 5/6 nephrectomized (5/6 Nx) rats. The rats were randomly divided into seven groups (n=10 per group) as follows: (i) 5/6 Nx (model group; 2.25 ml/kg/day normal saline); (ii) SKGL (low dose; 5/6 Nx treated with 2 g crude drug/kg/day SKG); (iii) SKGM (moderate dose; 5/6 Nx treated with 4 g crude drug/kg/day SKG); (iv) SKGH (high dose; 5/6 Nx treated with 8 g crude drug/kg/day SKG); (v) benazepril treatment group (5/6 Nx treated with 5 mg/kg/day benazepril); (vi) Shenkang injection (SKI) group (5/6 Nx with 13.3 ml/kg/day SKI); and (vii) sham-operated group (2.25 ml/kg/day normal saline). After 30 days, the levels of microalbumin, total protein, serum creatinine, blood urea nitrogen and serum lipid were found to be significantly decreased in the SKGL and SKGM rats, showing histological improvement compared with the untreated 5/6 Nx rats, as determined by hematoxylin and eosin, and Masson's trichrome staining. In addition, SKG was found to significantly improve the levels of glutathione peroxidase and reduce the damage caused by free radicals to the kidney tissues. Furthermore, SKG prevented the accumulation of extracellular matrix by decreasing the expression of collagen I and III and inhibiting the expression of matrix metalloproteinases-2 and -9 in the renal tissue, as determined by western blot analysis. SKG was also shown to decrease the concentrations of serum transforming growth factor-ß1, as determined by ELISA, and kidney angiotensin II, as determined using a radioimmunoassay kit. In conclusion, SKG was demonstrated to ameliorate renal injury in a 5/6 Nx rat model of CRF. Thus, SKG may exert a good therapeutic effect on CRF.

[Effect of Shenkang Injection on Kidney Function in Hypertensive Renal Damage Rats].

OBJECTIVE: To observe the effect of Shenkang Injection on the blood pressure, metabolism, blood biochemistry and renal pathology in hypertension renal damge rats, then to provide theoretical basis for clinical trials. METHODS: 75 spontaneously hypertensive nephropathy rats were randomly divided into five groups with 15 rats in each group: model group (SHR group) rats were intragastrically treated with the vehicle (4 mL/kg normal saline per day) of Shenkang Injection per day; Benazepril group( positive control group, 8 mg/ kg Benazepril per day) ;Shenkang Injection low-dose group (6.7 mL/kg Shenkang Injection per day); middle-dose group (13.3 mL/kg Shenkang Injection per day); high-dose group (26.6 mL/kg Shenkang Injection per day); and WKY rats were normal control group (n = 15) (4 mL/kg normal saline per day). RESULTS: After 3 months intraperitoneal injection treatment, SHR rats blood pressure were in- hibited; the levels of microalbumin (m-ALB), total protein (U-TP), serum creatinine (Ser) and urea nitrogen (BUN) were decreased significantly in Shenkang Injection treated groups rats. Shenkang Injection significantly improved the levels of creatinine clearance rate (Ccr), serum albumin (ALB) and superoxide dismutase (SOD), decreased the content of methane dicarboxylic aldehyde (MDA), aldosterone (Ald), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-ß1 (TGF-ß1) and C-reactive protein (CRP), and had histologic improvement compared with model group. CONCLUSION: Shenkang Injection can improve the kidney function, decrease the levels of serum inflammatory factors,improve the oxidative status and reduce the degree of hypertensive renal damage.

Chemical constituents from Trichilia connaroides and their nitric oxide production and α-glucosidase inhibitory activities.

Phytochemical investigation of the stem and bark of Trichilia connaroides led to the isolation of eight new nortriterpenoids (1-8), along with fifteen known compounds (9-23). Their structures were established based on extensive spectroscopic analysis. The absolute configuration of 2 was confirmed by X-ray crystallographic study. The nitric oxide production and α-glucosidase inhibitory effects for these isolates were evaluated: moderate to strong nitric oxide production inhibitory activities were found for 5, 6, and 11-15, with IC50 values ranging from 7.5 to 26.3 µM; marked α-glucosidase inhibitory effects were observed for 22 and 23, with IC50 values of 2.3 and 0.4 µM, respectively.

Monoterpene indole alkaloids from the stem bark of Mitragyna diversifolia and their acetylcholine esterase inhibitory effects.

Five monoterpene indole alkaloids, mitradiversifoline, with a unique rearranged skeleton, specionoxeine-N(4)-oxide, 7-hydroxyisopaynantheine, 3-dehydropaynantheine, and 3-isopaynantheine-N(4)-oxide, and 10 known ones, were isolated from Mitragyna diversifolia. All the isolates were evaluated for their inhibition of acetylcholinesterase activities, and four showed moderate activities, with IC50 values of 4.1, 5.2, 10.2, and 10.3 µM, respectively.

Imperatorin prevents cardiac hypertrophy and the transition to heart failure via NO-dependent mechanisms in mice.

Augmented endothelial nitric oxide (NO) synthase (eNOS) signaling has been reported to be associated with improvements in cardiac remodeling, and NO levels have been shown to be related to cardiac hypertrophy and heart failure. Imperatorin, a dietary furanocoumarin, has been shown to prevent cardiac hypertrophy in the spontaneous hypertension rats (SHR). Thus, we aimed to clarify whether imperatorin attenuates both cardiac hypertrophy and heart failure via the NO-signaling pathway. In neonatal mouse cardiac myocytes, imperatorin inhibited protein synthesis stimulated by either isoproterenol or phenylephrine, which was unchanged by NG-nitro-L-arginine methyl ester (L-NAME). Four weeks after transverse aortic constriction (TAC) on Kunming (KM) male mice, the ratio of heart weight to body weight was lower after imperatorin treatment than in controls (6.60 ± 0.35 mg/g in TAC, 4.54 ± 0.29 mg/g with imperatorin 15 mg kg(-1)d(-1), ig, P<0.01); similar changes in the ratio of lung weight to body weight (7.30 ± 0.85 mg/g in TAC, 5.42 ± 0.51 mg/g with imperatorin 15 mg kg(-1)d(-1), ig) and the myocardial fibrosis. All of these improvements were blunted by L-NAME. Imperatorin treatment significantly activated phosphorylation of eNOS. Myocardial mRNA levels of natriuretic peptide precursor type B and protein inhibitor of NO synthase, which were increased in the TAC mice, were decreased in the imperatorin-treated ones. Imperatorin can attenuate cardiac hypertrophy both in vivo and in vitro, and halt the process leading from hypertrophy to heart failure by a NO-mediated pathway.

Bioactivity-guided isolation of antiproliferative diterpenoids from Euphorbia kansui.

Cytotoxic assay guided multistep separation on the dichloromethane extract of the roots of Euphorbia kansui resulted in the isolation of 10 ingenol-type diterpenoids (1-4 and 7-12), of which, 5-O-(2'E,4'E-decadienoyl)-20-O-acetylingenol (1) is a new compound, and two are jatrophane-type diterpenoids (13-14). Interconversion of two pairs of positional ester isomers (1-4) in aqueous alcoholic solution was observed, the transesterification mechanism of which was speculated and confirmed by acylation of 3 and 4 to 6 and 5, respectively. All the isolates and the two acyl derivatives (5 and 6) were evaluated in vitro for their cytotoxicities in Bel-7402, Bel-7402/5FU, BGC-823 and SGC-7901 cell lines. The 12 ingenol-type diterpenoids exhibited weak to moderate cytotoxicities, whereas the two jatrophane-type diterpenoids displayed no antiproliferative effects, which, however, may increase the antitumour efficacy of those ingenol-type diterpenoids. The structure--activity relationships were investigated by principal component analysis (PCA) of the pIC50 (-logIC50) values of the compounds tested and their calculated molecular descriptors. The pIC50 values were highly correlated with most descriptors, especially the highest occupied molecular orbital energy (E(HOMO)), absolute hardness (η) and positively charged solvent accessible surface areas (P-ASA). As the values of E(HOMO) increase, η and P-ASA decrease, and the antiproliferative effects of these compounds increase.