One new 12, 8-guaianolide sesquiterpene lactone with antihyperglycemic activity from the roots of Cichorium intybus.

Three 12, 8-guaianolide sesquiterpene lactones, including a new compound intybusin F (1), and a new natural product cichoriolide I (2), along with six known 12, 6-guaianolide compounds (4-9) were isolated from the roots of Cichorium intybus L. Their structures were determined by extensive spectroscopic analysis. The absolute configurations of new compounds were elucidated based on analysis of the experimental and calculated electronic circular dichroism spectra. Compounds 1, 2, 4, 7, 8 showed significant effects on facilitating the glucose uptake in oleic acid plus high glucose-stimulated HepG2 cells at 50 µM. In addition, compounds 1, 2, 3, 6, 7 exhibited obvious inhibitory effects against NO production, of them, compounds 1, 2, 7 can significantly decrease the secretion of inflammatory cytokines (TNF-α, IL-6 and COX-2) levels in this hyperglycemic HepG2 cell model.

Sesquiterpene lactones with anti-inflammatory and cytotoxic activities from the roots of Cichorium intybus.

Cichorium intybus L. (Asteraceae), belonging to the tribe Cichorieae of the family Asteraceae, has a long history as an edible and medicinal food. Sesquiterpene lactones are commonly considered as its major active constituents. In the current study, five unreported sesquiterpene lactones, including one 12,8-guaianolide and four 12,6-guaianolides were isolated from C. intybus roots, as well as 16 known analogues. The planar structures and relative configurations of these compounds were elucidated by extensive spectroscopic analysis. The absolute configurations were determined by the time-dependent density functional theory (TDDFT)-based electronic circular dichroism (ECD) calculation method. Bioassay results showed that seven of the isolates exhibited remarkable NO production inhibitory activity in LPS-stimulated RAW264.7 macrophages, with IC50 values ranging from 1.83 to 38.81 µM. Some of them can significantly decrease the secretion of inflammatory cytokines (TNF-α and IL-6). Cytotoxicity assays demonstrated that intybusins B, as well as four known compounds, displayed obvious inhibitory activities against four human tumor cells, with IC50 values ranging from 9.01 to 27.07 µM.

Chicoric Acid Attenuated Renal Tubular Injury in HFD-Induced Chronic Kidney Disease Mice through the Promotion of Mitophagy via the Nrf2/PINK/Parkin Pathway.

As the main factor in the pathogenesis of chronic kidney disease (CKD), the excessive apoptosis of renal tubular epithelial cells (RTECs) and its underlying mechanism of action are worth further investigation. Chicoric acid (CA), a major active constituent of the Uyghur folk medicine chicory, was recorded to possess a renal protective effect. The precise effect of CA on renal tubular injury in obesity-related CKD remains unknown. In the current study, CA was proven to ameliorate metabolic disorders including overweight, hyperglycemia, hyperlipidemia, and hyperuricemia in high fat diet (HFD)-fed mice. Furthermore, the reverse effect of CA on renal histological changes and functional damage was confirmed. In vitro, the alleviation of lipid accumulation and cell apoptosis was observed in palmitic acid (PA)-exposed HK2 cells. Treatment with CA reduced mitochondrial damage and oxidative stress in the renal tubule of HFD-fed mice and PA-treated HK2 cells. Finally, CA was observed to activate the Nrf2 pathway; increase PINK and Parkin expression; and regulate LC3, SQSTM1, Mfn2, and FIS1 expression; therefore, it would improve mitochondrial dynamics and mitophagy to alleviate mitochondrial damage in RTECs of obesity-related CKD. These results may provide fresh insights into the promotion of mitophagy in the prevention and alleviation of obesity-related CKD.

Antitussive and expectorant properties of growing and fallen leaves of loquat (Eriobotrya japonica)

ABSTRACT Folium Eriobotryae, the dried leaves of loquat (Eriobotrya japonica, (Thunb.) Lindl., Rosaceae), is a traditional Chinese medicine used to treat cough with phlegm in China. Fallen and growing loquat leaves were tested for their effect on coughing and expectoration in mice. HPLC-ELSD and HPLC-MS analyses of aqueous and ethanol extracts of fallen or growing leaves were used to identify the chemical components responsible for this effect. Both the aqueous and ethanol extracts of growing and fallen leaves of loquat contained antitussive and expectorant activities. Moreover, an aqueous extract of growing loquat leaves with a higher flavonoid content displayed a stronger expectorant activity while the ethanol extract of fallen loquat leaves that contained a higher content of triterpenoid acids induced a stronger antitussive activity.

Investigation of the volatile constituents of different Gynura species from two Chinese origins by SPME/GC-MS.

GC-MS analyses of the volatile constituents obtained by solid phase microextraction (SPME) of two Gynura species, i.e., G. divaricata and G. bicolor, collected from Nanjing and Nanping areas in the east of China, enabled the identification of more than 50 different components. Generally, a higher contents of sesquiterpene compounds such as beta-caryophyllene, alpha-caryophyllene and alpha-copaene were found in G. bicolor than in G. divaricata, regardless of their origin. Qualitatively, the detected major volatiles of G. bicolor and G. divaricata originating from Nanjing were the same, i.e., beta-caryophyllene, alpha-caryophyllene, alpha-copaene, alpha-pinene and beta-pinene. The volatile profile of a third species, G. medica, also originating from Nanjing was different with sesquiterpenes gamma-cadinene, beta-caryophyllene, elixene and monoterpene limonene as the major components. The volatile profiles of G. bicolor and G. divaricata originating from Nanping were more diverse. For both species beta-caryophyllene, alpha-copaene and limonene were the major volatiles, but G. bicolor also produced gamma-caryophyllene and carvone as major constituents, whereas for G. divariata o-cymene was detected. Overall, these results indicate that the biosynthesis of volatiles by Gynura species is not only species related, but is also possibly influenced by the local environmental conditions of growth.

The anti-hyperglycemic effect of plants in genus Gynura Cass.

Gynura divaricata (L.) DC and G. bicolor DC are used as secret recipes to treat diabetes mellitus in some parts of China. Pharmacological tests were performed to prove the anti-hyperglycemic effect of these two plants of genus Gynura Cass. in this study. Both water and 95% ethanol extracts of fresh G. divaricata had significant effects on lowering blood glucose level in normal mice, in which the dose of 0.4 g (crude drug)/kg of 95% ethanol extract was more effective than 50 mg/kg glyburide. The ethyl acetate and n-butanol extracts of dried G. divaricata had significant effects on lowering blood glucose level in normal and alloxan diabetic mice too. Both ethyl acetate and n-butanol extracts of dried G. bicolor showed very significant effect on lowering blood glucose level to normal and alloxan-diabetic mice, and the dose 4.0 g (crude drug)/kg had a more hypoglycemic effect than 50 mg/kg glyburide in normal mice.

Euscaphic acid, a new hypoglycemic natural product from Folium Eriobotryae.

Folium Eriobotryae has been used as a medicinal plant for a long time, and it is known to have many physiological actions such as anti-inflammatory, anti-tussive, expectorant and anti-diabetic. We have reported that the 70% ethanol extract of Folium Eriobotryae exerted a significant hypoglycemic effect to alloxan-diabetic mice. In this study, we isolated euscaphic acid, a natural product from Folium Eriobotryae, and investigated its hypoglycemic effect in normoglycemic and alloxan-diabetic mice. All effects had been compared with those of gliclazide. The plasma glucose levels were significantly lowered in normoglycemic mice treated with euscaphic acid compared to mice treated with 0.5% CMC-Na solution only. Moreover, the dosage of 50 mg/kg exerted a significant (P < 0.05) hypoglycemic effect in alloxan-diabetic mice after orally administration. The research proved that euscaphic acid is one of the active hypoglycemic constituents in Folium Eriobotryae, but the details of the mechanism need to be investigated further.

Pharmacological studies on anti-hyperglycemic effect of folium eriobotryae.

Folium eriobotryae, dried leaves of Eriobotrya japonica (Thunb.) Lindl. is a traditional Chinese medicine with rich resources in China. This research investigated the anti-hyperglycemic effect of folium eriobotryae on normal and alloxan-diabetic mice. The 70% ethanol extract of folium eriobotryae (EJA-0) in doses of 15, 30 and 60 g (crude drug)/kg exerted a significant hypoglycemic effect on alloxan-diabetic mice, among which 30 g/kg of EJA-0 was more effective than 100 mg/kg of phenformin. The total sesquiterpenes (EJA-1) 30 g (crude drug)/kg had significant effect on lowering blood glucose level in normal or/and alloxan-diabetic mice. The tests of maximum dosage and acute toxicity showed that EJA-1 was safe (MD = 360 g/kg, LD(50) = 400.1 g/kg). The pharmacological tests on anti-hyperglycemic effects of EJA-0 and EJA-1 prove that folium eriobotryae is an outstanding material to develop medicine for treatment of diabetes mellitus.