Optimization of Ultrasound-Assisted Extraction of Polyphenols from Ilex latifolia Using Response Surface Methodology and Evaluation of Their Antioxidant Activity.

The polyphenolic extract of Ilex latifolia (PEIL) exhibits a variety of biological activities. An evaluation of the parameters influencing the ultrasonic extraction process and the assessment of PEIL antioxidant activity are presented herein. Response surface methodology (RSM) was used to optimize the experimental conditions for the polyphenols ultrasonic-assisted extraction (UAE) from the leaves of Ilex latifolia. We identified the following optimal conditions of PEIL: ethanol concentration of 53%, extraction temperature of 60 °C, extraction time of 26 min and liquid−solid ratio of 60 mL/g. Using these parameters, the UAE had a yield of 35.77 ± 0.26 mg GAE/g, similar to the value we predicted using RSM (35.864 mg GAE/g). The antioxidant activity of PEIL was assessed in vitro, using various assays, as well as in vivo. We tested the effects of various doses of PEIL on D-galactose induced aging. Vitamin C (Vc) was used as positive control. After 21 days of administration, we measured superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, malondialdehyde (MDA) levels in mouse serum and liver tissue. The results demonstrated that the PEIL exhibits potent radical scavenging activity against 1,1-diphenyl-2-picrythydrazyl (DPPH∙), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS+), and hydroxyl (∙OH) radicals. The serum concentrations of SOD and GSH-Px were higher, and MDA levels were lower, in the medium- and high-dose PEIL-treated groups than those in the aging group (p < 0.01), and the activity of MDA was lower than those of the model group (p < 0.01). The liver concentrations of SOD and GSH-Px were higher (p < 0.05), and MDA levels were lower, in the medium- and high-dose PEIL-treated groups than those in the aging control group (p < 0.01). These results suggest that optimizing the conditions of UAE using RSM could significantly increase the yield of PEIL extraction. PEIL possesses strong antioxidant activity and use as a medicine or functional food could be further investigated.

Discovery of an EGFR tyrosine kinase inhibitor from Ilex latifolia in breast cancer therapy.

Deficient signaling of the EGFR and other receptor tyrosine kinases in humans is associated with diseases such as cancer. Some EGFR tyrosine kinase inhibitors have become a new class of targeted therapeutic agents in the last years. We found that 27-O-p-(E)-coumaroyl ursolic acid (27-CAUA) had a strong activity of apoptosis according to preparation by screening for a series of Ilex latifolia products. 27-CAUA inhibited EGFR kinase system to lead to inactivation of PI3K/AKT/mTOR and Ras-Raf-MEK-ERK signal pathways which implicated in the proliferation and survival of tumor cells. These findings suggested that 27-CAUA was an orally active, selective epidermal growth factor receptor-tyrosine kinase inhibitor which could lead to beneficial manifestations in the clinic.

[27-O-(E)-p-coumaric acyl ursolic acid via JNK/SAPK signal pathway regulates apoptosis of human breast cancer MDA-MB-231 cell line].

27-O-(E)-p-coumaric acyl ursolic acid( DY-17) from Ilex latifolia is a compound of the monomer. To investigate the DY-17 inducing apoptosis in the human breast cancer cell line, the MDA-MB-231 cells were used as research object in this experiment. The proliferation activity of the MDA-MB-231 cells stimulated with the different concentrations of DY-17 (20, 40 µmol · L(-1)) was detected at different time( 12, 24, 36, 48, 60,72 h) . We surveyed the DY-17 inducing apoptosis of the MDA-MB-231 cells with the fluorescent staining technology. The rate of MDA-MB-231 cells apoptosis and necrosis was determined by flow cell cytometry (FCC). Moreover, expression of JNK, phosphorylated JNK, Bax, PARP shear and caspase-3 shear related to JNK/SAPK pathways were investigated in every group ( control group, EGF group, EGF + DY-17 40 µmol · L(1) group and EGF + SP600125 group) with Western blot. The MTT results showed that, in the presence of DY-17, the proliferation activity of MDA-MB-231 cells decreased in a dose-dependent and time-dependent manner. The apoptosis and necrosis rates of MDA-MB-231 cells with DY-17(20, 40 µmol · L(-1)) groups was respectively 31.86%, 49.91% by flow cytometry and significantly increased compared with control group under Fluores- cence microscopy. Up-regulation of the JNK phosphorylation protein expression was observed in EGF group compared with control group. In addition, markedly decreased the expression of JNK phosphorylation protein were also surveyed in EGF + DY-17 40 µmol · L(-1) group compared with EGF group. The expression of Bax, shear PARP and shear caspase-3 protein in EGF + DY-17 40 µmol · L(-1) group were significantly increased in comparison with EGF group. The results showed DY-17 induced apoptosis of human breast cancer MDA-MB-231 cell line related to down-regulating JNK/SAPK signal pathways.

[Triterpenoids from Leaves of Ilex latifolia].

OBJECTIVE: To investigate the chemical constituents from the leaves of Ilex latifolia. METHODS: The constituents were iso- lated and purified by various chromatographic techniques. Their structures were identified by UV, IR, MS and NMR spectroscopic analy- sis. RESULTS: Ten compounds were isolated from the leaves of flex latifolia. Their structures were respectively identified as 3ß,13ß-Di- hydroxy-urs-11-en-28-oic acid-13-lactone (1), ß-sitosterol (2) 3-hydroxy-11-oxours-12-ene (3), (20S,24S)-epoxydammarane-3ß,25- diol (4), 25-deuteriostigmasterol (5), α-amyrin (6), foliasalacin A4 (7), 23-hydroxyursolic acid (8), p-coumaric acid (9) and ß-dau- costerol (10). CONCLUSION: Compounds 1,3-5,7 and 9 are isolated from this plant for the first time.

[Chemical constituents from leaves of Ilex latifolia].

Nine compounds were isolated from the leaves of Ilex latifolia. Their structures were respectively identified as 5-hydroxy-6, 7, 8, 4'-tetramethoxyflavone (1), tangeretin (2), nobiletin (3), 5-hydroxy-6, 7, 8, 3', 4'-pentamethoxyflavone (4), 5, 6, 7, 8, 4'-pentamethoxyflavonol (5), 5, 6, 7, 8, 3', 4'-hexamethoxy-flavonol (6), 5-hydroxy-3', 4', 7-trimethoxyflavanone (7), soyacerebroside I (8), and soyacerebroside II (9) by their physicochemical properties and spectroscopic data Compounds 1-9 were isolated from this plant for the first time.

[Quality assessment on schisandrae fructus from different habitats].

OBJECTIVE: To assay five lignans in Schisandrae Fructus collected from different habitats. METHODS: HPLC method was developed to assay Schizandrol A, Schizandrol B, Schisantherain A, deoxyschizandrin and gamma-schizandrin in Schisandrae Fructus. Hierarchical clustering analysis (HCA) and principal components analysis (PCA) were performed to evaluate and classify 30 batches of samples based on the contents of the five lignans using SOLO and SPSS 19.0 software. RESULTS: 30 batches of samples were divided into three groups, which reflecting their quality characteristics. CONCLUSION: PCA and HCA provide the basis for the classification and quality evaluation of Schisandrae Fructus. The content analysis provides reference for resources saving and rational using of Schisandrae Fructus.

Advancing herbal medicine: enhancing product quality and safety through robust quality control practices.

This manuscript provides an in-depth review of the significance of quality control in herbal medication products, focusing on its role in maintaining efficiency and safety. With a historical foundation in traditional medicine systems, herbal remedies have gained widespread popularity as natural alternatives to conventional treatments. However, the increasing demand for these products necessitates stringent quality control measures to ensure consistency and safety. This comprehensive review explores the importance of quality control methods in monitoring various aspects of herbal product development, manufacturing, and distribution. Emphasizing the need for standardized processes, the manuscript delves into the detection and prevention of contaminants, the authentication of herbal ingredients, and the adherence to regulatory standards. Additionally, it highlights the integration of traditional knowledge and modern scientific approaches in achieving optimal quality control outcomes. By emphasizing the role of quality control in herbal medicine, this manuscript contributes to promoting consumer trust, safeguarding public health, and fostering the responsible use of herbal medication products.

ERBB2 promoter demethylation and immune cell infiltration promote a poor prognosis for cancer patients.

Background: Receptor tyrosine-protein kinase erbB-2 (ERBB2) expression is a critical factor for the prognosis of various cancers. ERBB2 enrichment indicates a poor prognosis in some cancer types but could be a favorable prognostic factor in others. Methods: We analyzed DNA methylation, mRNA, protein, immune cell infiltration, and related signaling pathways using TIMER2.0, GEPIA2, STRING, and UALCAN portal datasets in tumor tissues of diverse cancer types and their matched normal tissues. Results: ERBB2 promoter demethylation increases transcript protein amplification and promotes a poor prognosis for cancer patients. ERBB2 gain-of-function procures immune cell infiltration for tumor growth and drives away T regulatory cells, which suppress or downregulate induction and proliferation of effector T cells. The downstream signaling pathways, such as tumor proliferation, ECM-related genes, and degradation of ECM, are involved in ERBB2 gene demethylation and immune activation in cancer progression. Conclusion: ERBB2 gene demethylation leads to a poor prognosis in cancer patients, which is strongly influenced by the composition and abundance of tumor immune cell infiltration. ERBB2 demethylation could be used in clinical practice to identify immune profiles and direct therapeutic strategies.

A Link Between Chemical Structure and Biological Activity in Triterpenoids.

BACKGROUND: Plants that are rich in triterpenoid compounds possess various biological activities and are reported in many scientific works. Triterpenoids, because of their broad sources, wide variety, high medicinal value, and anti-tumor properties, have drawn great attention from scientists. However, the lack of approach to understand the link between their chemical structures and biological activities has limited the fundamental comprehension of these compounds in cancer therapy. OBJECTIVE: The aim of the study is to summarize the list of plants with triterpenoids and their derivatives that are a source of potential novel therapeutic anti-cancer agents by interpreting the network of anti-cancer activity and the structures of triterpenoids and their derivatives. METHODS: This work focuses on analyzing relevant patents and references that detail the structure of triterpenoids and their derivatives for the treatment of tumors. RESULTS: Pentacyclic triterpenoid plays a more important role in improving the autophagic signaling pathways of cancer cells compared to tetracyclic triterpenoid. CONCLUSION: The heterogenous skeleton structure of triterpenoids impairs programmed cell death signaling pathways in various cancers.

[Study on seed morphology of the section Cruciata Gaudin].

OBJECTIVE: To provide a scientific evidence for the identification of the section Cruciata Gaudin. METHODS: Seed morphology of the section Cruciata Gaudin in different regions from Gansu were studied by means of scanning electronic microscopy (SEM). RESULTS: The seeds of section Cruciata Gaudin had relative conformability in terms of shape,size and ornamentation. But the reticulate cell of Gentiana dahurica was obviously wider than those of other species. CONCLUSION: This study provides some useful information for classification and identification of section Cruciata Gaudin.

[Textual research and surveying on officinal varieties of rhizoma arisaematis].

Through textual research and surveying on officinal varieties of Rhizoma Arisaematis, we considered the following results. The name of Rhizoma Arisaematis is in ceaseless change and its original is in confusion in the development of bencaology history. The original plants as Rhizoma Arisaematis are from many species and have wide distribution. This review can provide important reference for exploitation and utilization of resources and further development of Rhizoma Arisaematis through the discussion of the state of its original plant, distribution and mainstream varieties in the current market.

Four new triterpenes and triterpene glycosides from the leaves of Ilex latifolia and their inhibitory activity on triglyceride accumulation.

Two new triterpenes (1 and 2) and two new triterpene glycosides (3 and 4), along with six known triterpenes (5-10) were isolated from the leaves of Ilex latifolia. The structures of new compounds were elucidated on the basis of NMR, HR-MS, and X-ray diffraction analysis. Compounds 4 and 5 showed potent inhibitory activity on oleic acid/palmitic acid induced triglyceride accumulation on HepG2 cells.

Ilelic acids A and B, two unusual triterpenes with a seven-membered ring from Ilex latifolia.

Two unusual triterpenes, ilelic acids A (1) and B (2), together with their biosynthetic related compounds ilelic acids C (3) and D (4) were isolated from the leaves of Ilex latifolia. Their structures with absolute configurations were elucidated by spectroscopic analysis and modified Mosher's method. The plausible biogenetic pathway of 1 and 2 is proposed. These triterpenes exhibited a potent inhibitory effect on MCF-7 and MDA-MB-231 cells.