Integrating network pharmacology and experimental validation to explore the effect and mechanism of AD-1 in the treatment of colorectal cancer.

20 (R)-25-methoxyl-dammarane-3ß, 12ß, 20-triol (AD-1), a novel ginsenoside isolated from stem and leaf of Panax Notoginseng, has anticancer activity against a variety of malignant tumors. However, the pharmacological mechanism of AD-1 on colorectal cancer (CRC) remains unclear. The purpose of this study was to verify the potential mechanism of action of AD-1 against CRC through network pharmacology and experiments. A total of 39 potential targets were obtained based on the intersection of AD-1 and CRC targets, and key genes were analyzed and identified from the PPI network using Cytoscape software. 39 targets were significantly enriched in 156 GO terms and 138 KEGG pathways, among which PI3K-Akt signaling pathway was identified as one of the most enriched pathways. Based on experimental results, AD-1 can inhibit the proliferation and migration of SW620 and HT-29 cells, and induce their apoptosis. Subsequently, the HPA and UALCAN databases showed that PI3K and Akt were highly expressed in CRC. AD-1 also decreased the expressions of PI3K and Akt. In summary, these results suggest that AD-1 can play an anti-tumor role by inducing cell apoptosis and regulating PI3K-Akt signaling pathway.

New Phenolic Dimers from Plant Paeonia suffruticosa and Their Cytotoxicity and NO Production Inhibition.

The Paeonia suffruticosa, known as 'Feng Dan', has been used for thousands of years in traditional Chinese medicine. In our chemical investigation on the root bark of the plant, five new phenolic dimers, namely, paeobenzofuranones A-E (1-5), were characterized. Their structures were determined using spectroscopic analysis including 1D and 2D NMR, HRESIMS, UV, and IR, as well as ECD calculations. Compounds 2, 4, and 5 showed cytotoxicity against three human cancer cell lines, with IC50 values ranging from 6.7 to 25.1 µM. Compounds 1 and 2 showed certain inhibitory activity on NO production. To the best of our knowledge, the benzofuranone dimers and their cytotoxicity of P. suffruticosa are reported for the first time in this paper.

Optimization of Extraction and Separation Process of Notoginsenoside Fc from Panax notoginseng Leaves.

Response surface methodology (RSM) was used to determine the optimal conditions for ultrasound-assisted extraction (UAE) of Notoginsenoside Fc (Fc) from panax notoginseng leaves. The experiment utilized a Box-Behnken design (BBD) and separation conditions were optimized. The optimum extraction conditions were as follows: extraction time = 1.5 h, ethanol concentration = 86%, liquid-to-solid ratio = 19:1. The experimentally obtained values were in accordance with the values predicted by the RSM model. We determined that the RSM model was able to successfully simulate the optimal extraction of Fc from the leaves. Further, Fc was enriched from Panax notoginseng through nine macroporous resins, and HPD-100 macroporous resins were selected for preliminary enrichment of Fc due to its economic costs and benefits. Subsequently, octadecyl silane (ODS) column chromatography was used to improve the purity of Fc to over 90% after separation by ODS column chromatography. Fc with a purity greater than 95% can be obtained by recrystallization. This is the first study that has focused on the extraction and enrichment of Fc from Panax notoginseng leaves using macroporous resin combined with ODS column chromatography, which provides the possibility for further application of Fc.

Nine New Pregnane Glycosides from the Cultivated Medicinal Plant Marsdenia tenacissima.

The ethnobotanical plant Marsdenia tenacissima has been used for hundreds of years for Dai people in Yunnan Province, China. Previously, chemical investigations on this plant have revealed that pregnane glycosides were the main biological constituents. Nine new pregnane glycosides, marsdeosides A-I (1-9), were isolated from cultivated dried stems of the medicinal plant Marsdenia tenacissima in this study. The structures were analyzed by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and IR spectroscopic analysis. The absolute configurations of the sugar moieties were identified by comparing the Rf values and specific optical rotations with those of the commercially available standard samples and the data reported in the literature. Marsdeosides A (1) featured an unusual 8,14-seco-pregnane skeleton. Compounds 1, 8, and 9 showed activity against nitric oxide production in lipopolysaccharide-activated macrophage RAW264.7, with IC50 values of 37.5, 38.8, and 42.8 µM (L-NMMA was used as a positive control, IC50 39.3 µM), respectively. This study puts the knowledge of the chemical profile of the botanical plant M. tenacissima one step forward and, thereby, promotes the sustainable utilization of the resources of traditional folk medicinal plants.

Effects of dietary wild bitter melon (Momordica charantia var. abbreviate Ser.) extract on glucose and lipid metabolism in HFD/STZ-induced type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Plant-based extracts to interfere with the onset of diabetes may be a promising approach towards type 2 diabetes mellitus (T2DM). Bitter gourd (Momordica charantia L.) is popularly consumed as an edible and medicinal resource with hypoglycemic effect in China. Wild bitter gourd (Momordica Charantia var. abbreviata Ser.) is a variant of bitter gourd, but there are relatively few studies on it. AIM OF THE STUDY: The purpose of the experiment is to first screen out the most effective extraction part of Momordica charantia L. and Momordica Charantia var. abbreviata Ser. through the hypoglycemic activity experiment 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: This study first performed α-glucosidase, PTP1B and lipase activities inhibition experiments on the alcohol and water extracts of Momordica charantia L. and Momordica Charantia var. abbreviata Ser. 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, treatments were administered for four weeks, and then blood samples were used to evaluate hematological and biochemical indicators, and liver was removed for post-analysis. The expression levels of p-AMPK, AMPK, p-PI3K, PI3K, p-AKT, AKT, p-GSK3ß, GSK3ß, p-IRS-1, IRS-1, GLUT2 were determined by Western blot. At the same time, the chemical components was identified by liquid-mass spectrometry. RESULTS: Data showed that the ethanol extract of wild bitter gourd (WBGE) had the best ability to regulate glucose and lipid metabolism in vitro. Therefore, we further investigated the antidiabetic effects of oral consumption of WBGE on high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in SD rats. WBGE effectively reduced blood glucose and lipid levels, alleviated glucose intolerance and insulin resistant. Moreover, WBGE consumption could also inhibited oxidant responses and inflammatory damage. Mechanism studies have shown that WBGE may act by regulating AMPK/PI3K signaling pathway. On the other hand, the content of total phenol, total flavonoids, total saponins and total polysaccharide were measured by UV, 27 compounds were identified by LC-MS. CONCLUSIONS: These studies explored the role and mechanism of WBGE in regulating glucose and lipid metabolism, and may support the utilization and further investigation of wild bitter gourd as a dietary intervention strategy to prevent diabetes and related metabolic abnormalities.

Two new iridoid glycosides from Odontites vulgaris.

Two new iridoid glycosides, named 3'-O-benzoyl-dolichocymboside D (1) and dolichocymboside E (2), along with ten known glycosides (3-12), were isolated from the ethanol extract of the whole plants of Odontites vulgaris Moench. The structures of the isolated compounds were elucidated by 1D and 2D NMR and HR-ESI-MS spectra and by comparison with those reported in the literature. This is the first report on compounds 11 and 12 isolated from the family Scrophulariaceae, and compounds 8-10 were isolated from the genus Odontites.

Design, synthesis, and biological evaluation of novel protopanoxadiol derivatives based PROTACs technology for the treatment of lung cancer.

Protopanoxadiol is a key active ingredient derived from Panax ginseng that is well-known to exhibit anti-tumor activity. Previous research focused on the natural protopanaxadiol derivative AD-1 has demonstrated that it possesses broad spectrum anti-tumor activities in vitro and in vivo. However, its limited activity, selectivity, and cell permeability have impeded its therapeutic application. Herein, a series of novel AD-1 derivatives were designed and synthesized based on proteolysis-targeting chimera (PROTAC) technology by linking AD-1 at the C-3 and C-12 positions with pomalidomide through linkers of alkyl chain of differing lengths to achieve the goal of improving the efficacy of the parent compound. Among these synthesized PROTACs, the representative compound A05 exhibited the most potent anti-proliferative activity against A549 cells. Furthermore, mechanistic studies revealed that compound A05 was able to suppress MDM2 expression, disrupt interactions between p53 and MDM2 and readily induce apoptotic death via the mitochondrial apoptosis pathway. Moreover, the in vivo assays revealed that compound A05 exhibited both anti-proliferative and anti-metastatic activities in the zebrafish tumor xenograft model with A549 cells. Together, our findings suggest that AD-1 based PROTACs associated with the degradation of MDM2 may have promising effects for the treatment of lung cancer and this work provide a foundation for future efforts to develop novel anti-tumor agents from natural products.

Effects of Different Extraction Methods in Pharmacopoeia on the Content and Structure Transformation of Ginsenosides.

Ginseng (Panax ginseng C. A. Meyer), a perennial herb, possesses immunostimulatory, anticarcinogenic, antiemetic, and antioxidative biological activities. In recent years, more and more people have paid attention to the extraction methods and quality evaluation of ginseng. China, the United States, Europe, Japan, and Korea have all had the quality standards and content determination methods of ginseng. The different treatment methods are adopted before the determination of ginseng samples and the content limits of the index components, such as ginsenoside Rb1, ginsenoside Rg1, and ginsenoside Re exist differences. The similarities and differences of ginseng content detection methods in pharmacopoeias of different countries have been analyzed by a research group, but the comparison of the effects of different methods on the ginsenoside content and structural transformation has not been reported. In this paper, ginsenosides in ginseng were extracted according to four national pharmacopoeias and analyzed quantitatively and qualitatively by UPLC-Q-Exactive-MS and HPLC-UV. It was illustrated that the pretreatment method has a significant influence on the content determination of ginseng. The yield of rare saponins was increased by heating concluded from both the qualitative and quantitative comparison. Finally, a simple and feasible extraction method was optimized by response surface method at room temperature. The analysis of the preparation method and process optimization of the four pharmacopoeias can provide important reference information for the revision of ginseng standards.

Gypensapogenin I Suppresses Cell Proliferation in Triple-Negative Breast Cancer Via Triggering the Closure of AKT/GSK3ß/ß-Catenin and Notch-1 Signaling Pathways.

Jiaogulan (Gynostemma pentaphyllum) tea is a functional food that is commercially available worldwide. Gypensapogenin I (Gyp I), which is a natural damarane-type saponin, was obtained from the hydrolysates of total gypenosides. The present research was performed to investigate the potential antiproliferation effect of Gyp I in MDA-MB-231 cells and the underlying mechanisms. Here, we found that Gyp I attenuated survival, inhibited proliferation, and induced apoptosis in MDA-MB-231 cells. Target prediction by binding molecule docking and western blot assays confirmed the mechanism by which Gyp I inhibited the proliferation of breast cancer cells via the AKT/GSK3ß/ß-catenin signaling pathway. We also showed that Gyp I exhibited superior in vivo efficacy that was dose dependent. Tumor tissue transcriptome analysis indicated that Gyp I could decrease the expression levels of NOTCH1 and HES1, which was in contrast to the effect on MAML and NUMBL, indicating that our compound hindered the activation of the Notch-1 signaling pathway. In summary, we report for the first time that Gyp I shows excellent anti-breast cancer activity in vivo and in vitro and that its pathway of action is related to the AKT/GSK3ß/ß-catenin and Notch-1 signaling pathways. Therefore, Jiaogulan tea can not only be used as a health food but also possesses the possibility to treat triple-negative breast cancer (TNBC).

Deciphering the spatial-temporal transcriptional landscape of human hypothalamus development.

The hypothalamus comprises various nuclei and neuronal subpopulations that control fundamental homeostasis and behaviors. However, spatiotemporal molecular characterization of hypothalamus development in humans is largely unexplored. Here, we revealed spatiotemporal transcriptome profiles and cell-type characteristics of human hypothalamus development and illustrated the molecular diversity of neural progenitors and the cell-fate decision, which is programmed by a combination of transcription factors. Different neuronal and glial fates are sequentially produced and showed spatial developmental asynchrony. Moreover, human hypothalamic gliogenesis occurs at an earlier stage of gestation and displays distinctive transcription profiles compared with those in mouse. Notably, early oligodendrocyte cells in humans exhibit different gene patterns and interact with neuronal cells to regulate neuronal maturation by Wnt, Hippo, and integrin signals. Overall, our study provides a comprehensive molecular landscape of human hypothalamus development at early- and mid-embryonic stages and a foundation for understanding its spatial and functional complexity.

Flash extraction of the active constituents and its antitumor activity from rehmanniae radix, achyranthes bidentatae radix, dioscoreae rhizoma and chrysanthemi flos.

In this study, we applied the Flash extraction (FE) for the first time to the extraction of active ingredients of Sidahuaiyao (including Rehmanniae Radix, Achyranthes Bidentatae Radix, Dioscoreae Rhizoma, and Chrysanthemi Flos), and the content of active ingredients (catalpinoside, ecdysterone, chlorogenic acid and diosgenin) was determined by HPLC, and compared with Soxhlet extraction (SE) and ultrasonic extraction (UE). The results show that under the same solvent ratio, FE is used to extract the largest amount of different active ingredients. Compared with SE and UE, the extraction amount increases by 20.8% -92%. It is demonstrated for the first time that using FE to extract the active ingredients from Sidahuaiyao produced the highest extraction efficiency. In addition, we evaluated the anticancer activities of the main components. Three cancer cells and one normal cells were used to detect the anti-proliferative activity by MTT assay. The results showed that diosgenin had the strongest inhibitory effect on MCF-7 cells with IC50 value of 19.28±0.36µM. In short, we optimized the extraction process of Sidahuaiyao, and evaluated the anti-cancer activity of the main components, which provided a scientific theoretical basis for the application of Sidahuaiyao.

Activity Components from Gynostemma pentaphyllum for Preventing Hepatic Fibrosis and of Its Molecular Targets by Network Pharmacology Approach.

Hepatic fibrosis would develop into cirrhosis or cancer without treating. Hence, it is necessary to study the mechanism and prevention methods for hepatic fibrosis. Gynostemma pentaphyllum is a traditional medicinal material with a high medicinal and health value. In this study, nineteen compounds obtained from G. pentaphyllum were qualitative and quantitative by HPLC-FT-ICR MS and HPLC-UV, respectively. Among them, the total content of 19 gypenosides accurately quantified reaches 72.21 mg/g and their anti-proliferation against t-HSC/Cl-6 cells indicated compound 19 performed better activity (IC50: 28.1 ± 2.0 µM) than the other compounds. Further network pharmacology study demonstrated that compound 19 mainly plays an anti-fibrosis role by regulating the EGFR signaling pathway, and the PI3K-Akt signaling pathway. Overall, the verification result indicated that compound 19 appeared to be nontoxic to LO2, was able to modulate the PI3K/Akt signal, led to subG1 cells cycle arrest and the activation of mitochondrial-mediated apoptosis of t-HSC/Cl-6 cells for anti-hepatic fibrosis.

Anti-hepatic fibrosis effects of AD-2 affecting the Raf-MEK signaling pathway and inflammatory factors in thioacetamide-induced liver injury.

25-Hydroxylprotopanaxadiol-3ß, 12ß, 20-triol (25-OH-PPD or AD-2) belongs to dammarane ginsenoside, and is commonly obtained from the acidic hydrolysate of total ginsensides of Panax ginseng. This study investigated the potential mechanism of AD-2 toward improving thioacetamide (TAA)-induced hepatic fibrosis in mice. Mice were divided into seven groups: control group, TAA model group, TAA + AD-2 (5, 10, and 20 mg/kg) groups, TAA + silymarin (100 mg/kg) group, and TAA + Fu Fang Biejia (FFBj; 300 mg/kg) group. All mice were treated to intraperitoneal TAA injection to establish a hepatic fibrosis model, and drugs were administered orally. The mechanism and related pathways underlying the AD-2-mediated action against hepatic fibrosis were explored by Western blotting and immunohistochemical staining. After AD-2 treatment, the expression levels of Lipin-1, SREBP1, and F4/80 significantly decreased, meanwhile the protein expressions levels of IL1ß, IL1R1, IL18, Bax, Bid, Bcl-2, and cFlips also decreased. Furthermore, AD-2 inhibited RAF and MEK pathways. The results demonstrate that AD-2 can alleviate hepatic fibrosis. The mechanism is likely related to the regulation of lipid accumulation, inflammatory response, apoptosis pathway, and Raf-MEK signaling pathways, which provide a basis for clinical research for the treatment of hepatic fibrosis. PRACTICAL APPLICATION: Ginsenoside is one of the main active ingredients of ginseng, and can alleviate the symptoms of various diseases, for example, hepatic fibrosis. This paper mainly used Western blotting to explore its possible mechanism of action. The goal was to provide a reference for the development of traditional Chinese medicines for hepatic fibrosis.

ChaiQi Decoction Alleviates Vascular Endothelial Injury by Downregulating the Inflammatory Response in ApoE-Model Mice.

Metabolic syndrome (MetS) is a pathological state of metabolic disorders that primarily occur in human proteins, fats, and carbohydrates. It is a complex cluster of core metabolic disorder syndromes including obesity, hyperglycemia, dyslipidemia, and hypertension, and vascular endothelial injury, occurring over time. The currently available treatment options cannot effectively manage MetS. In our previous research, we revealed ChaiQi decoction (CQD) as an effective prescription for improving MetS; however, the specific mechanism remains unclear. Herein, we assessed the efficacy and mechanism of CQD in ApoE gene knockout (ApoE-) mice. Mice were administered with CQD daily for 12 weeks, and the measurement of their body weight was taken monthly. To evaluate the metabolic levels of mice, we determined the fasting blood glucose (FBG), fasting serum insulin (FINS), insulin resistance index (IRI), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels. Furthermore, immunohistochemical analysis was adopted to determine the expression of ICAM-1 and VCAM-1 in vascular endothelium, while an optical microscope was adopted to observe the pathological morphology of abdominal aorta in mice. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) levels were determined using the ELISA method, whereas Western blotting was used to determine nuclear factor- (NF-) κB p65. Of note, intragastric CQD administration ameliorated ApoE-model mice, as evidenced by reduced levels of FBG, FINS, IRI, TG, TC, and LDL-C. Furthermore, CQD alleviated vascular endothelial injury and regularized the structure of the abdominal aorta by downregulating the expressions of proinflammatory cytokines TNF-α, IL-6, ICAM-1, VCAM-1, and NF-κB p65. Overall, these findings advocated that CQD ameliorates metabolic levels and vascular endothelial injury in mice by downregulating the inflammatory response and thus may be utilized as a novel MetS therapy.

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.

The anti-tussive, anti-inflammatory effects and sub-chronic toxicological evaluation of perilla seed oil.

BACKGROUND: Perilla seed oil (PSO) is the main constituent of perilla seeds currently being used in the food industry, however it also has great clinical potential in the regulation of lung function as a nutrition supplement because of the high content of α-linolenic acid (ALA). In this study, the pharmacological activities including anti-tussive, expectorant and anti-inflammatory effect of PSO were performed. Furthermore, the 90-day sub-chronic oral toxicity with a 30 day recovery period was evaluated in Wistar rats. RESULTS: The pharmacological studies demonstrated that PSO inhibited cough frequency induced by capsaicine in mice. PSO also inhibited the leukotriene B4 (LTB4) release from the calcium ionophore A23187-induced polymorphonuclear neutrophils (PMNs) to some extent. In this sub-chronic toxicity study, mortality, clinical signs, body weight, food consumption, hematology, serum biochemistry, urinalysis, organ weight, necropsy, and histopathology were used to evaluate the toxicity of PSO. Lower body weight and various negative impacts on liver related parameters without histopathological lesion were observed in the 16 g kg-1 groups. No clinically significant changes were discovered in the 4 g kg-1 group during the test period. CONCLUSION: In summary, PSO exhibited anti-tussive and anti-inflammatory activities in vivo and in vitro. These sub-chronic toxicity studies inferred that the 'no-observed adverse effect level' (NOAEL) of PSO in Wistar rats was determined to be 4 g kg-1 . These results may provide a safety profile and a valuable reference for the use of PSO. © 2020 Society of Chemical Industry.

The effects of linalool acupoint application therapy on sleep regulation.

The Shenque acupoint is located in the umbilicus of the human body. In the human body meridians, the Shenque acupoint can regulate body functions. The Shenque acupoint was one of the important acupuncture acupoints for the treatment of insomnia. However, the effect of linalool applied at the Shenque acupoint to improve sleep was unknown. This study explored the hypnotic and sedative effects of the main component of lavender, linalool, on the Shenque acupoint of mice and rats. The effects on the sleep latency and sleep duration were studied with the supra-threshold dose of pentobarbital sodium, and the effects on the sleep rate were studied with the sub-threshold dose of pentobarbital sodium. In order to further study the feasibility and superiority of linalool administered at the Shenque acupoint, a pharmacokinetic study was carried out. The pharmacodynamic results showed that the mice and rats treated with linalool at Shenque had the highest sleep rate, the shortest sleep latency, and the longest sleep duration compared with other groups. The T max and t 1/2 of the LS were longer than those of the LO, and had the characteristics of sustained release. The relative bioavailability of LS was 323.0 ± 31.66%. This showed that the combination of linalool and the Shenque acupoint had greater medicinal effects. This development will provide a new direction for improving sleep.

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.