Betulinic acid inhibits the proliferation of human laryngeal carcinoma cells through reactive oxygen species-mediate mitochondrial apoptotic pathway.

Betulinic acid (BA), a natural pentacyclic triterpene, was extracted from the white birch tree, Triphyophyllum peltatum and the jujube tree. In a variety of human cancer cell lines, this substance displays anticancer properties. In this study, we examined how BA works to inhibit human laryngeal cancer growth. We discovered that BA minimally exhibited cytotoxicity in normal cells (human normal cell line GES-1), while remarkably inhibiting viability of AMC-HN-8, TU212, HEp-2 and M4e cells in a concentration-dependent manner. In AMC-HN-8 cancer cells, BA induced apoptosis, activated caspase-3/9/PARP, significantly reduced mitochondrial membrane potential (MMP), increased the expression of cytochrome C in the cytoplasm, transported Bax to the mitochondria, increased the production of reactive oxygen species (ROS), and the ROS scavenger N-acetylcysteine can reduce apoptosis. All data showed that BA triggered apoptosis via the mitochondrial pathway, in which ROS production was likely involved. The findings support the development of BA as a viable drug for the treatment of human laryngeal carcinoma.

Stereospecificity of Ginsenoside AD-1 and AD-2 Showed Anticancer Activity via Inducing Mitochondrial Dysfunction and Reactive Oxygen Species Mediate Cell Apoptosis.

In this paper, the anti-cancer activity and molecular mechanisms of the isomers of AD-1 and AD-2 (20(R)-AD-1, 20(R)-AD-2, 20(S)-AD-1 and 20(S)-AD-2) were investigated. The results indicated that all of the four compounds obviously suppressed the viability of various cancer cells, and the anti-cancer activity of 20(R)-AD-1 and 20(R)-AD-2 was significantly better than 20(S)-AD-1 and 20(S)-AD-2, especially for gastric cancer cells (BGC-803). Then, the differences in the anti-cancer mechanisms of the isomers were investigated. The data showed that 20(R)-AD-1 and 20(R)-AD-2 induced apoptosis and decreased MMP, up-regulated the expression of cytochrome C in cytosol, transferred Bax to the mitochondria, suppressed oxidative phosphorylation and glycolysis and stimulated reactive oxygen species (ROS) production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. However, 20(S)-AD-1 and 20(S)-AD-2 barely exhibited the same results. The results indicated that 20(R)-AD-1 and 20(R)-AD-2 suppressed cellular energy metabolism and caused apoptosis through the mitochondrial pathway, which ROS generation was probably involved in. Above all, the data support the development of 20(R)-AD-1 and 20(R)-AD-2 as potential agents for human gastric carcinoma therapy.

Real-time observation of stationary and pulsating noise-like vector pulses in a fiber laser.

Rapid progress in real-time measurement technology has uncovered varieties of transient pulse dynamics. Here, we report the vector nature of noise-like pulse (NLP) in a passive fiber laser based on the nonlinear optical loop mirror (NOLM) as the polarization independent saturable absorber. After achieving the basic operation regime of NLP, various types of vector pulses, namely, the polarization locked noise-like vector pulse (PLNLVP), the group velocity locked noise-like vector pulse (GVLNLVP), and the transitional state of combined characteristics of GVLNLVP and polarization rotation noise-like vector pulse (PRNLVP) are also obtained in the cavity. Besides, by utilizing the Dispersive Fourier transform (DFT) technique, the spectral evolution and the energy vibration of pulsating PLNLVP, GVLNLVP, and the transitional state of combined characteristics of GVLNLVP and PRNLVP are also analyzed in real time. Particularly, the coexisting pulsation vector state of NLP and soliton is also captured. All these findings will help to complement our understanding of noise-like vector pulses (NLVPs) in a fiber laser.

A combined network pharmacology and molecular biology approach to investigate the potential mechanisms of G-M6 on ovarian cancer.

Ginsenoside 3ß,12ß,21α,22ß-Hydroxy-24-norolean-12-ene (G-M6), a phase I metabolite of anti-tumor medication 20(R)-25-methoxyl-dammarane-3ß,12ß,20-triol (AD-1), beats the parent drug in anti-ovarian cancer efficacy. The mechanism of action for ovarian cancer, however, is uncertain. Using network pharmacology, human ovarian cancer cells and nude mouse ovarian cancer xenotransplantation model, the anti-ovarian cancer mechanism of G-M6 was preliminarily explored in this study. The PPAR signal pathway is the key signal pathway of the G-M6 anti-ovarian cancer mechanism, according to data mining and network analysis. Docking tests demonstrated that the bioactive chemical G-M6 was capable of forming a stable bond with the PPARγ target protein capsule. Using human ovarian cancer cells and xenograft model of ovarian cancer to evaluate the anticancer activity of G-M6. The IC50 value of G-M6 was 5.83±0.36, lower than AD-1 and Gemcitabine. The tumor weight of the RSG 80 mg/kg group (C), G-M6 80 mg/kg group (I), and RSG 80 mg/kg + G-M6 80 mg/kg group (J) after the intervention was as follows: C < I < J. The tumor inhibition rates of groups C, I, and J were 28.6%, 88.7%, and 92.6%, respectively. When RSG and G-M6 are combined to treat ovarian cancer, q = 1.00 is calculated according to King's formula, which indicates that RSG and G-M6 have additive effects. Its molecular mechanism may involve the up-regulation of PPARγ and Bcl-2 protein expressions, and the down-regulation of Bax, Cytochrome C (Cyt. C), Caspase-3, and Caspase-9 protein expressions. These findings serve as a reference for further research into the processes behind ginsenoside G-M6's ovarian cancer therapy.

Quantifying emission fluxes of atmospheric pollutants from mobile differential optical absorption spectroscopic (DOAS) observations.

This study demonstrates a mobile passive differential optical absorption spectroscopy (DOAS) based remote sensing method for quantifying the emission fluxes of soot pollutants. First, the mobile DOAS system scans the plume emitted from urban sources. Then, the DOAS method retrieves the total columns of pollutant gases along the measurement path. Combining the longitude, latitude, and mobile speed recorded by vehicle GPS, the net emission fluxes of NO2 and SO2 in the measurement area are calculated by coupling with the wind field data. The NO2 flux in the region is combined with the NO to NO2 concentration ratio in the Copernicus Atmospheric Monitoring Service (CAMS) model to calculate NOx net emission flux in the measurement period. We conducted the mobile DOAS measurements in the coal production area and obtained the distribution of pollutant gases along the measurement path. Meanwhile, the NO2 concentration distribution of the city and surrounding areas were reconstructed by using TROPOMI satellite data. During the mobile measurement, the net NO2 emission flux measured by mobile DOAS are in good agreement with satellite observations (R2 = 0.66). This study verified that the flux calculation method based on mobile DOAS can be used to detect urban soot pollutant gas emissions.

Polyketides with anti-inflammatory activity isolated from Rhodiola tibetica endophytic fungus Penicillium sp. HJT-A-10.

Seven undescribed polyketide compounds (1-4, 9-11) and six known polyketide compounds (5-8,12, 13) were isolated from Rhodiola tibetica endophytic Penicillium sp. HJT-A-10. The structural of seven undescribed polyketides metabolites were established on the basis of spectroscopic methods. The results of anti-inflammatory activity showed that compounds 1-8，10-13 had significant inhibitory effects on LPS-induced NO production in RAW 264.7 cells.

Polyketides with anti-inflammatory activity from Rhodiola tibetica endophytic fungus Alternaria sp. HJT-Y7.

Seven undescribed polyketides with particular ortho-trisubstituted benzo[c]furan and benzo[c]oxepin spiro structures were isolated from Rhodiola tibetica endophytic fungus Alternaria sp. HJT-Y7. Structural elucidations of these compounds were determined mainly by NMR and HR-ESI-MS analysis. An assumed polyketide biosynthetic pathway of these isolates was proposed. Two undescribed compounds and four known compounds showed significant inhibitory effects on LPS-induced NO production in RAW 264.7 cells without cytotoxicity at their effective concentrations.

Novel ginsenoside derivatives have shown their effects on PC-3 cells by inducing G1-phase arrest and reactive oxygen species-mediate cell apoptosis.

In this study, piperazine groups were introduced into ginsenoside to enhance its ability to induce Reactive Oxygen Species (ROS) production and apoptosis in cancer cells. In total, 27 ginsenoside piperazine derivatives were synthesized and tested for their anti-proliferative activity in cancer cell lines by MTT assay. The results showed that compounds 4a, 4g, 4f, 4i, 5g, 5i, 6a, 6g, 6f and 6i had significant inhibitory effects on cancer cell growth. Compound 6g showed the strongest anti-proliferative effect on PC-3 cells with an IC50 of 1.98 ± 0.34 µM. Compound 6g could also induce G1-phase arrest and apoptosis in PC-3 cells, with apoptosis rates of 8.1%, 41% and 56.1% observed at 5, 10 and 20 µM, respectively. Compound 6g also significantly enhanced the intracellular fluorescence of ROS sensitive substrates, with a fluorescence intensity ratio of 23.1% observed in treated cells, indicative of ROS production. Following N-acetylcysteine treatment, apoptotic rates of the cancer cell lines decreased from 38.9% to 7.3%, and the expression of Cl-PARP, Cl-Caspase-3 and Cl-Caspase-9 also decreased, confirming that compound 6g induced apoptosis through ROS induction. Compound 6g also stimulated the translocation of Bax from the cytoplasm to the mitochondria, which enhanced Cytochrome C (Cyt C) release, and increased the expression of the apoptotic markers Cl-PARP, Cl-Caspase-3, and Cl-Caspase-9 in PC-3 cells. Taken together, these data reveal the anti-cancer effects of compound 6g that enhance ROS production, and then induce apoptosis through mitochondrial pathway.

Multiple Roles of Black Raspberry Anthocyanins Protecting against Alcoholic Liver Disease.

This study aimed to investigate the protective effect of black raspberry anthocyanins (BRAs) against acute and subacute alcoholic liver disease (ALD). Network analysis and docking study were carried out to understand the potential mechanism. Thereafter, the serum biochemical parameters and liver indexes were measured, the histopathological changes of the liver were analyzed in vivo. The results showed that all tested parameters were ameliorated after the administration of BRAs with alcohol. Meanwhile, there was increased protein expression of NF-κB and TGF-ß in extracted livers, which was associated with hepatitis and hepatic fibrosis. Furthermore, BRAs and cyanidin-3-O-rutinoside exhibited cytotoxic effects on t-HSC/Cl-6, HepG2, and Hep3B and induced the apoptosis of HepG2 cells; downregulated the protein expression level of Bcl-2; upregulated the level of Bax; and promoted the release of cytochrome C, cleaved caspase-9, cleaved caspase-3, and cleaved PARP in HepG2 cells. In addition, the antioxidant activity of BRAs was tested, and the chemical components were analyzed by FT-ICR MS. The results proved that BRAs exert preventive effect on ALD through the antioxidant and apoptosis pathways.

Ameliorative effect of white tea from 50-year-old tree of Camellia sinensis L. (Theaceae) on kidney damage in diabetic mice via SIRT1/AMPK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic kidney damage (DKD) is one of the most common complications of diabetes, which is known as a chronic inflammatory kidney disease caused by persistent hyperglycemia. White tea was originally used as a folk medicine to treat measles in ancient China. What arouses our interest is that there is a traditional method to treat diabetes with white tea taken from over 30-year-old tree of Camellia sinensis L. However, there are few reports on the renal protection of white tea. AIM OF THE STUDY: This present study was designed to study the potential protective effects of white tea (WT) and old tree white tea (OTWT) on high-fat-diet (HFD) combined with streptozotocin (STZ)-induced type 2 diabetic mice to explore the possible mechanism of WT/OTWT against DKD. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into four groups: NC, T2D, WT (400 mg/kg·b.w, p.o.), OTWT (400 mg/kg·b.w, p.o.). Diabetes was established in all groups except NC group, by six weeks of HFD feeding combined with STZ (50 mg/kg, i.p.) for 3 times, treatments were administered for six weeks and then all the animals were decapitated; kidney tissues and blood samples were collected for the further analysis, including: levels of insulin, lipid metabolism (TG, TC, HDL, LDL, FFA), antioxidative enzymes (catalase (CAT), super oxide dismutase (SOD), glutathione peroxidase (GPx)), blood urea nitrogen (BUN) and creatine, inflammatory cytokines (TNF-α, IL-1ß, COX-2, iNOS, MCP-1), advanced glycation end products (AGE), receptor of AGE (RAGE), Nrf2, AMPK, SIRT1, and PGC-1α. H&E, PAS and Masson staining were performed to examine the histopathological alterations of the kidneys. RESULTS: Our data showed that WT and OTWT reversed the abnormal serum lipids (TG, TC, HDL, LDL, FFA) in T2D mice, upregulated antioxidative enzymes levels (CAT, SOD, GPx) and inhibit the excessive production of proinflammatory mediators (including MCP-1, TNF-α, IL1ß, COX-2 and iNOS) by varying degrees, and OTWT was more effective. In histopathology, OTWT could significantly alleviate the accumulation of renal AGE in T2D mice, thereby improving the structural changes of the kidneys, such as glomerular hypertrophy, glomerular basement membrane thickening and kidney FIbrosis. CONCLUSIONS: Both WT and OTWT could alleviate the diabetic changes in T2D mice via hypoglycemic, hypolipidemic, anti-oxidative and anti-inflammatory effects, while OTWT was more evident. OTWT could prominently alleviate the accumulation of AGE in the kidneys of T2D mice, thereby ameliorating the renal oxidative stress and inflammatory damage, which was associated with the activation of SIRT1/AMPK pathway.

Combination of white tea and peppermint demonstrated synergistic antibacterial and anti-inflammatory activities.

BACKGROUND: White tea, considered to be the oldest form of tea, is becoming a popular beverage for its organoleptic characteristics. Peppermint tea, used as a herbal remedy for centuries, is now also very popular throughout the world as herbal tea. What interested us was that in ancient China, peppermint was used in combination with tea as a detoxification or anti-inflammatory agent. However, there are few reports on the combined use of white tea and peppermint. Therefore, this study aims to investigate the antibacterial and anti-inflammatory activities of white tea in combination with peppermint. RESULTS: A synergistic inhibitory effect against four bacterial strains, especially against Staphylococcus argenteus, was observed in the combination of white tea and peppermint in vitro. In addition, the combined formula demonstrated a stronger anti-inflammatory effect in vivo than either of the two used alone, which was associated with the decrease of the pro-inflammatory cytokines of interleukin-6 (IL-6), interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In a further mechanism study, it was found that white tea and peppermint inhibited the phosphorylation of p-IκB-α and mitogen-activated protein kinase (MAPK) at different degrees. While the enhanced anti-inflammatory effect of the combined formula was associated with the combination of NF-κB down-regulation and p-MAPK inhibition. CONCLUSION: In our study, it was for the first time shown that when white tea was combined with peppermint, the antibacterial and anti-inflammatory effects were enhanced. The results suggested an effective application of white tea in combination with peppermint as a potential antibacterial and anti-inflammatory functional food. © 2020 Society of Chemical Industry.

Protective effect of acorn (Quercus liaotungensis Koidz) on streptozotocin-damaged MIN6 cells and type 2 diabetic rats via p38 MAPK/Nrf2/HO-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Acorn obtained from the Quercus liaotungensis Koidz tree is consumed as a Chinese folk medicine for the treatment of diarrhea, abdominal pain, and inflammation, also having strong antioxidant activity and have been utilized for the treatment of diabetes in China. However, its mechanism of action on complications of diabetes and oxidative stress is unclear. AIM OF THE STUDY: The purpose of this research was to assess the effects of acorn (Quercus liaotungensis Koidz) ethanol extract (AE) on pancreatic ß-cell dysfunction through a streptozotocin (STZ)-damaged mouse normal pancreatic ß-cell (MIN6 cell) model in vitro, and by using a high-fat and high-sugar diet with STZ-induced diabetic rat model in vivo to explore the possible mechanism of action against diabetes. MATERIALS AND METHODS: MIN6 cells were pretreated with AE (20, 40, 80 µM) for 2 h and then treated with 3 mM STZ for 24 h. Cell viability was measured by MTT assay. The amount of intracellular reactive oxygen species was measured by 2,7-dichlorodi-hydrofluorescein diacetate. The activities of insulin secretion, superoxide dismutase, catalase and glutathione were determined by kits. Sprague Dawley rats were either given normal feed or a high sugar and fat diet for four weeks, followed STZ (25 mg/kg, via i. p.) was given. Rats with fasting blood glucose ≥11.1 mmol/l after one week were deemed to be diabetic. Animals were divided into 5 groups, which received saline (10 mL/kg), metformin (200 mg/kg), or AE at doses of 200 and 400 mg/kg during 4 weeks by oral gavage. Blood samples were used to evaluate hematological and biochemical indicators, and pancreas was removed for post-analysis. Body weight and fasting blood glucose were recorded weekly. The expression levels of Bax, Bcl-2, p38, p-p38, Nrf2 and HO-1 were determined by Western blot. RESULTS: Data showed that AE inhibited apoptosis and increased antioxidant level in STZ-induced MIN6 cells. In addition, the AE-administered group lowered blood glucose, increased insulin secretion, and alleviated weight loss in the diabetic rats. Histopathologically, the AE-administered group reduced pancreatic injury by significantly restoring the insulin content in ß-islets. It was observed that the anti-diabetic effects of AE were associated with the suppressed the p38 MAPK pathway and actived the Nrf2 pathway. CONCLUSIONS: The ameliorative impact of AE on diabetes may be attributed to protection of the function of pancreatic ß islets and by improving serum insulin levels, hence reducing the blood glucose, which involved in the p38 MAPK and Nrf2 pathways.

Dietary Ginsenoside T19 Supplementation Regulates Glucose and Lipid Metabolism via AMPK and PI3K Pathways and Its Effect on Intestinal Microbiota.

Ginseng, as a functional food, is widely used worldwide because of its multifarious benefits. Studies have verified that 25-hydroxyl-protopanaxatriol (T19) is a new ginsenoside from ginseng, which had an important inhibitory effect on α-glucosidase and protein tyrosine phosphatase 1B in vitro. This study aims to assess the regulation of T19 against glycolipid metabolism by insulin-resistant HepG2 cells and diabetes mice induced with high-fat diet combined with streptozotocin (STZ). T19 effectively lowered the levels of blood glucose and lipid, alleviated insulin resistance, and improved histological pathology of liver and pancreas. Further study demonstrated that regulation of AMP-activated protein kinase- and phosphoinositide-3-kinase-signaling pathways was involved in the potential mechanism of T19 efficiency. Simultaneously, high-throughput sequencing of 16S rDNA revealed that T19 remarkably ameliorated the high-fat diet/STZ-induced disorders of intestinal microbiota by decreasing the value of Firmicutes/Bacteroidetes, and remarkably raised the relative abundance of the Lachnospiraceae family, which are the beneficial bacteria that can regulate glucose and lipid metabolism. The results may provide clues for further understanding the mechanism of T19 in regulating glycolipid metabolism, and may provide a scientific basis for ginseng as a potential dietary food to prevent metabolic diseases.

Rational design, synthesis and biological evaluation of triphenylphosphonium-ginsenoside conjugates as mitochondria-targeting anti-cancer agents.

In anti-cancer therapy, targeting a single gene or a single metabolic pathway usually cannot effectively cure cancer, while targeting cellular mitochondria might be effective based on the role of mitochondria in the occurrence and development of cancer. Anti-cancer study on ginsenosides AD-1, AD-2 and PD have proved that they have broad spectrum anti-cancer activities in vitro and in vivo. However, they are not active at sufficiently low concentration, and their lower selectivity and cell permeability hindered therapeutic applications. In the present study, AD-1, AD-2 and PD are incorporated with triphenylphosphonium at the OH group in C-3 position through different length of alkyl chains, with the aim of targeting mitochondria and improving the efficacy and selectivity of parent compounds. Biological studies suggested that most of the conjugates had enhanced anti-proliferative activity, in particular, conjugate 1f had an IC50 value of 0.76 µM against MCF-7 cells while showed a high degree of selectivity to MCF-7 cells. In addition, 1f was obviously increased accumulation in the mitochondria, and induced apoptosis, elevated reactive oxygen species (ROS) level and caused mitochondrial membrane potential collapse in MCF-7 cells. Further study revealed that ROS-related mitochondrial translocation of p53 was also involved in 1f-induced mitochondrial apoptotic pathway. The results demonstrated that 1f could be a promising lead for the development of mitocans. These findings also provide a reference for the development of ginsenoside for mitochondria-targeted anti-cancer drugs.

Novel panaxadiol triazole derivatives induce apoptosis in HepG-2 cells through the mitochondrial pathway.

In this study, we introduced 1, 2, 4-triazole groups into panaxadiol (PD) to obtain 18 panaxadiol triazole derivatives. Five cancer cells and one normal cell were evaluated for cytotoxicity by MTT assay. The results showed that most of the derivatives could inhibit cancer cell proliferation, and the anti-proliferative activity of compound A1 was the most significant. For HepG-2 cells, the IC50 value was 4.21 ± 0.54 µM, which was nearly 15 times higher than the activity of PD. Further studies showed that compound A1 could induce apoptosis in HepG-2 cells, and could enhance the expression of Cl-caspase-3, Cl-caspase-9 and Cl-PARP. Moreover, Western blot analysis showed that after treating HepG-2 cells with compound A1, the expression of p53 protein was increased and the ratio of Bax/Bcl-2 was gradually increased. The cytoplasmic Bax is then translocated to the mitochondria, causing the release of Cyt c protein. Therefore, the results indicate that compound A1 induces apoptosis through the mitochondrial pathway and can be used the potential to develop new anti-proliferative agents.

3ß-Hydroxysteroid-Δ24 Reductase (DHCR24) Protects Pancreatic ß Cells from Endoplasmic Reticulum Stress-Induced Apoptosis by Scavenging Excessive Intracellular Reactive Oxygen Species.

There is accumulating evidence showing that apoptosis induced by endoplasmic reticulum (ER) stress plays a key role in pancreatic ß cell dysfunction and insulin resistance. 3ß-Hydroxysteroid-Δ24 Reductase (DHCR24) is a multifunctional enzyme located in the endoplasmic reticulum (ER), which has been previously shown to protect neuronal cells from ER stress-induced apoptosis. However, the role of DHCR24 in type 2 diabetes is only incompletely understood so far. In the present study, we induced ER stress by tunicamycin (TM) treatment and showed that infection of MIN6 cells with Ad-DHCR24-myc rendered these cells resistant to caspase-3-mediated apoptosis induced by TM, while cells transfected with siRNAs targeting DHCR24 were more sensitive to TM. Western blot analysis showed that TM treatment induced upregulation of Bip protein levels in both cells infected with Ad-LacZ (the control group) and Ad-DHCR24-myc, indicating substantial ER stress. Cells infected with Ad-LacZ exhibited a rapid and strong activation of ATF6 and p38, peaking at 3 h after TM exposure. Conversely, cells infected with Ad-DHCR24-myc showed a higher and more sustained activation of ATF6 and Bip than control cells. DHCR24 overexpression also inhibited the generation of intracellular reactive oxygen species (ROS) induced by ER stress and protected cells from apoptosis caused by treatment with both cholesterol and hydrogen peroxide. In summary, these data demonstrate, for the first time, that DHCR24 protects pancreatic ß cells from apoptosis induced by ER stress.

Jiaogulan tea (Gpostemma pentaphyllum) potentiates the antidiabetic effect of white tea via the AMPK and PI3K pathways in C57BL/6 mice.

The use of plant-based beverages to interfere with the onset of diabetes may be a promising approach towards type 2 diabetes mellitus (T2DM). The present study investigated the antidiabetic effects of the oral consumption of white tea and G. pentaphyllum (Jiaogulan), especially their combination on HFD/STZ-induced T2DM in C57BL/6 mice. White tea and Jiaogulan administration could mitigate glycolipid metabolic disorders in the diabetic mice by different degrees. White tea administration markedly reduced the blood glucose and ameliorated the glucose intolerance compared to the T2DM mice. Moreover, white tea consumption could protect the islet ß-cells against oxidative and inflammatory damage, related to the Nrf-2 signaling pathway. Jiaogulan prominently attenuated liver lipid accumulation by downregulation of SREBP levels. However, interestingly, when white tea was used in combination with Jiaogulan, these effects were enhanced to a certain extent. In particular, the combination significantly suppressed the hepatic G6Pase expressions by activating the AMPK pathway, thus inhibiting gluconeogenesis and improving insulin resistance. On the other hand, the combined formula could regulate the PPAR expressions and ameliorate the hepatic inflammation, further activating the IRS/PI3K/AKT pathway and exerting the antidiabetic potential. Therefore, it was speculated that the antidiabetic effect of this combination may be associated with the AMPK/PI3K pathways. Our findings might provide insight into the combined use of white tea with Jiaogulan tea as a potential functional beverage or food for preventing T2DM.

Synthesis of triterpenoid derivatives and their anti-tumor and anti-hepatic fibrosis activities.

Oleanolic acid (1), ursolic acid (2), hederagenin (3), betulinol (4), betulinic acid (5), and glycyrrhetinic acid (6) are obtained from acorn/licorice industrial wastes with common triterpenoid structure as a model set for esterification. Eight 3,4,5-methoxybenzoyl triterpenoid derivatives (1a-6a), including four new derivatives (1a, 3a-1, 3a-2, and 3a-3), are synthesized by classical procedures. Their antitumor and anti-hepatic fibrosis activities are evaluated on four human tumor cell lines and t-HSC/Cl-6 cells. Derivative 1a shows maximum antiproliferative effects against all cell lines, especially against tumor cells with IC50 values in the range of 5.32-15.23 µM, but does not affect the viability of normal cells. The anti-tumor mechanisms of 1a are also investigated by western blot and docking studies. The 3,4,5-methoxybenzoyl triterpenoids offers an intriguing solution for naturally derived antitumor drugs and may be invaluable for further development of cancer therapy.

Synthesis and anti-cancer activity studies of dammarane-type triterpenoid derivatives.

Two series of novel derivatives of AD-2, an active ginsenoside derived from ginseng were designed and synthesized. Five human cancer cell lines (MGC-803, SGC-7901, A549, MCF-7, PC-3 cells) and one normal ovarian cell IOSE144 were employed to evaluate the anti-proliferative activity. Most of derivatives possessed obvious enhanced activity compared with AD-2. Among them, compound 4c displayed the most excellent activity in all tested cancer cell lines, especially A549 cells with an IC50 value of 1.07 ± 0.05 µM. The underlying mechanism study suggested that 4c induced S-phase arrest and apoptosis in A549 cells. Increasing the level of ROS and inducing collapse of MMP in cells treated with 4c were also proved. Moreover, Western blot analysis showed that the expression level of p53 and p21 were obviously increased. 4c could remarkably up-regulate the expression of cyt c in cytosol, the ratio of Bax to Bcl-2 and activate caspase-3/9/PARP. Besides, the expression level of MDM2 was remarkably decreased. The results indicated that 4c caused apoptosis through the mitochondrial pathway, which ROS generation was probably involved in, and had the potent to serve as anti-proliferative agent.

Synthesis and Cytotoxicity Evaluation of Panaxadiol Derivatives.

In this study, 13 panaxadiol (PD) derivatives were synthesized via reactions with aromatic compounds and amino acids. Following this, the cytotoxicity of these compounds was evaluated against four cancer cell lines (human hepatoma cells HepG-2, human lung cancer cells A549, human breast cancer cells MCF-7, and human colon cancer cells HCT-116) and one normal cell lines (human gastric epithelial cells GES-1). The results showed that the panaxadiol derivatives 3, 12, and 13 showed significant inhibition of cellular proliferation against cancer cells compared with PD, and the panaxadiol derivative 12 had the lowest IC50 value for A549 (IC50 =18.91±1.03 µm). For MCF-7 cells, most compounds exhibited good inhibition of cellular proliferation, and the panaxadiol derivative 13 showed the strongest inhibitory effect (IC50 =8.62±0.23 µm), which significantly increased the cytotoxicity of PD and was stronger than the positive control (mitomycin). For normal cells, all compounds exhibited low or no toxic effects; thus, these derivatives can be used to develop novel antiproliferative agents.