Triptolide exposure induces oxidative stress and decreases oocyte quality in mouse.

Triptolide is a major active ingredient isolated from the traditional Chinese medicine Tripterygium wilfordii, which has anti-inflammatory, anti-cancer, and immunomodulatory effects. However, in clinical studies, triptolide has toxic side effects on the heart, kidney, liver and reproductive organs. With respect to female reproductive toxicity, damaging effects of triptolide on the ovary have been reported, but it has remained unknown whether oocytes are affected by triptolide. Therefore, this study established a concentration gradient of triptolide exposure in mice using 0 (control), 30, 60, and 90 µg triptolide/kg body weight/day administered by gavage. Triptolide administration for 28 d reduced body weight and ovarian weight and affected the developmental potential of oocytes. The triptolide-treated group exhibited meiotic failure of oocytes due to impaired spindle assembly, chromosome alignment, and tubulin stability. Triptolide was also found to induce mitochondrial dysfunction, autophagy and early apoptosis, iron homeostasis, and abnormal histone modifications. These adverse effects could be associated with oxidative stress induced by triptolide. In conclusion, our findings suggest detrimental effects of triptolide on mouse oocytes and, thus, on female reproduction.

A Chinese classical prescription Guizhi-Fuling Wan in treatment of ovarian cancer: An overview.

Ovarian cancer is one of the three most common female reproductive system cancers and has been a hot topic in the field of gynecology and oncology. Currently, surgery with chemotherapy is the common strategy in treatment of ovarian cancer, while it is always accompanied by drug resistance and some adverse effects. Over the past few years, traditional Chinese medicine (TCM) has been embraced by a large population of clinicians and researchers due to its high efficiency, low toxicity and minor side effects. Guizhi-Fuling Wan as a classical TCM formula has manifested certain efficacy in treating ovarian cancer. This article intends to further study the role and mechanism of Guizhi-Fuling Wan in treatment of ovarian cancer and explore the effective chemical components contained in the herbs of the formula. To this end, we reviewed the previous clinical studies and experiments to analyze the molecular mechanisms, pharmacological effects, active chemical components and their targets of action in treatment of ovarian cancer, thereby providing a theoretic basis for future studies and practices.

A Novel 5-HT1B Receptor Agonist of Herbal Compounds and One of the Therapeutic Uses for Alzheimer's Disease.

The serotonin receptor 5-HT1B is widely expressed in the central nervous system and has been considered a drug target in a variety of cognitive and psychiatric disorders. The anti-inflammatory effects of 5-HT1B agonists may present a promising approach for Alzheimer's disease (AD) treatment. Herbal antidepressants used in the treatment of AD have shown functional overlap between the active compounds and 5-HT1B receptor stimulation. Therefore, compounds in these medicinal plants that target and stimulate 5-HT1B deserve careful study. Molecular docking, drug affinity responsive target stability, cellular thermal shift assay, fluorescence resonance energy transfer (FRET), and extracellular regulated protein kinases (ERK) 1/2 phosphorylation tests were used to identify emodin-8-O-ß-d-glucopyranoside (EG), a compound from Chinese medicinal plants with cognitive deficit attenuating and antidepressant effects, as an agonist of 5-HT1B. EG selectively targeted 5-HT1B and activated the 5-HT1B-induced signaling pathway. The activated 5-HT1B pathway suppressed tumor necrosis factor (TNF)-α levels, thereby protecting neural cells against beta-amyloid (Aß)-induced death. Moreover, the agonist activity of EG towards 5-HT1B receptor, in FRET and ERK1/2 phosphorylation, was antagonized by SB 224289, a 5-HT1B antagonist. In addition, EG relieved AD symptoms in transgenic worm models. These results suggested that 5-HT1B receptor activation by EG positively affected Aß-related inflammatory process regulation and neural death resistance, which were reversed by antagonist SB 224289. The active compounds such as EG might act as potential therapeutic agents through targeting and stimulating 5-HT1B receptor for AD and other serotonin-related disorders. This study describes methods for identification of 5-HT1B agonists from herbal compounds and for evaluating agonists with biological functions, providing preliminary information on medicinal herbal pharmacology.

C21, C22 pregnane glycosides and cytotoxic C27 spriostanol steroids from Asparagus cochinchinesis.

A preliminary chemical investigation on 70% MeOH extract of the roots of Asparagus cochinchinensis resulted in the isolation of nine steroids. These isolates comprised of four new C21 (1-4) and one new pregnane (5) glycosides, and four known C27 (6-9) spirostanol steroids. Their structures were identified via analysis of the spectroscopic data and the results of hydrolytic cleavage. The cytotoxic activities of the compounds were tested toward the human tumor cell line Hela (cervical cancer), and compounds 7 and 8 displayed moderate activity with IC50 values of 35.5 and 39.6 µM, respectively.

Coix lacryma-jobi Seed Oil Reduces Fat Accumulation in Nonalcoholic Fatty Liver Disease by Inhibiting the Activation of the p-AMPK/SePP1/apoER2 Pathway.

The lipid metabolism disorder is the key role of Nonalcoholic fatty liver disease (NAFLD). Selenoprotein P plays an important role in the pathological process of lipid accumulation. Coix lacryma-jboi seed oil (CLSO) is an active component extracted from Coix lacryma-jobi seed (CLS) which has been found to be effective of reducing blood fat and antioxidative. But the effect and mechanism of CLSO on NAFLD are not clear. The aim of this study was to explore the therapeutic effect and mechanism of CLSO in the treatment of NAFLD. Our result showed that CLSO decreased the liver/body weight ratio, lowered the total cholesterol (TC) and triacylglycerol (TG), and elevated the high density lipoprotein (HDL) in serum. CLSO reduced the lipid deposition in the liver of NAFLD rats. In addition, CLSO could bring down the abnormal expression of superoxide dismutase (SOD) and malondialdehyde (MDA). Moreover, CLSO significantly declined the liver apolipoprotein E (apoE), apolipoprotein E receptor (apoER) and selenoprotein P 1 (SePP1) expression. In vivo, CLSO decreased the lipid droplets and TG level, reduced the protein expression of SePP1, apoER, phosphor-adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) in the cytoplasm of HepG2 cells induced by oleic acid and palmitic acid (OP). At the same time, lipid accumulation was observed in the Sepp1 high expression cells induced by endoplasmic reticulum (ER) activator tunicamycin (Tm). CLSO could identically reduce the protein expression of SePP1, apoER, p-AMPK in the cytoplasm of HepG2 cells induced by Tm. This result not only proved the CLSO had therapeutic effect on NAFLD, but also confirmed its mechanism associated with degrading the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) which led to the decrease of the expression SePP1/apoER2 in order to reduce lipid accumulation. The study suggests CLSO has great medicinal value in treating NAFLD besides its edibility.

Association of folate intake and plasma folate level with the risk of breast cancer: a dose-response meta-analysis of observational studies.

Epidemiological studies showing the correlation between folate and the breast cancer risk have revealed inconsistent results. Hence, we conducted a dose-response meta-analysis of observational studies to obtain more reliable conclusions. We searched PubMed and Embase for studies published before April 2019 and identified 39 studies on folate intake and 12 studies on plasma folate level. The combined odds ratios (ORs) and 95% confidence intervals (CIs) were extracted to estimate the breast cancer risk. Folate intake was inversely correlated with the breast cancer risk when the highest and lowest categories (OR = 0.85, 95% CI = 0.79-0.92) were compared, and the dose-response result showed that folate intake had a linear correlation with the breast cancer risk. Moreover, a higher folate intake correlated with a lower breast cancer risk in premenopausal women (OR = 0.80, 95% CI = 0.66-0.97), but not in postmenopausal women (OR = 0.94, 95% CI = 0.83-1.06). However, plasma folate levels were not correlated with the breast cancer risk (OR = 0.98, 95% CI = 0.82-1.17). Folate intake was negatively correlated with the breast cancer risk; however, its practical clinical significance requires further study. Furthermore, additional folate supplements should be considered carefully.

Identification of poliumoside metabolites in rat plasma, urine, bile, and intestinal bacteria with UPLC/Q-TOF-MS / 中国天然药物

Poliumoside is representative of phenylethanoid glycosides, which are widely found in many plants. Poliumoside is also regarded as the main active component of Callicarpa kwangtungensis Chun (CK), though its oral bioavailability in rat is extremely low (0.69%) and its in vivo and in vitro metabolism has not yet been systematically investigated. In the present study, an ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method was employed to identify the metabolites and investigate the metabolic pathways of poliumoside in rat after oral administration 1.5 g·kg of poliumoside. As a result, a total of 34 metabolites (30 from urine, 17 from plasma, and 4 from bile) and 9 possible metabolic pathways (rearrangment, reduction, hydration, hydrolyzation, dehydration, methylation, hydroxylation, acetylation, and sulfation) were proposed in vivo. The main metabolite, acteoside, was quantified after incubated with rat intestinal bacteria in vitro. In conclusion, the present study systematically explored the metabolites of poliumoside in vivo and in vitro, proposing metabolic pathways that may be significant for further metabolic studies of poliumoside.

Identification of poliumoside metabolites in rat plasma, urine, bile, and intestinal bacteria with UPLC/Q-TOF-MS / 中国天然药物

Poliumoside is representative of phenylethanoid glycosides, which are widely found in many plants. Poliumoside is also regarded as the main active component of Callicarpa kwangtungensis Chun (CK), though its oral bioavailability in rat is extremely low (0.69%) and its in vivo and in vitro metabolism has not yet been systematically investigated. In the present study, an ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method was employed to identify the metabolites and investigate the metabolic pathways of poliumoside in rat after oral administration 1.5 g·kg of poliumoside. As a result, a total of 34 metabolites (30 from urine, 17 from plasma, and 4 from bile) and 9 possible metabolic pathways (rearrangment, reduction, hydration, hydrolyzation, dehydration, methylation, hydroxylation, acetylation, and sulfation) were proposed in vivo. The main metabolite, acteoside, was quantified after incubated with rat intestinal bacteria in vitro. In conclusion, the present study systematically explored the metabolites of poliumoside in vivo and in vitro, proposing metabolic pathways that may be significant for further metabolic studies of poliumoside.

Chalcane-stilbene conjugates and oligomeric flavonoids from Chinese Dragon's Blood produced from Dracaena cochinchinensis.

A detailed chemical investigation of Chinese Dragon's Blood, which is a traditional medicine produced form the red resin of Dracaena cochinchinensis, yielded two chalcane-stilbene conjugates, named cochinchinenenes G and H, together with 25 known compounds. The structures of these compounds were determined by spectroscopic examination. HPLC analysis of the resin indicated that the major constituents were a complex mixture of oligomeric polyphenols, which were detected as a broad hump on the base line of a HPLC chromatogram. (13)C NMR analysis indicated that the oligomers were mainly composed of oxygenated chalcane units. This suggestion was supported by the results of a thiol degradation experiment with mercaptoethanol, which yielded a thioether of 4-[(4-hydroxyphenyl)propyl]-3-methoxyphenol. Furthermore, methylation followed by electrospray ionization mass spectroscopic analysis of the resulting fractions established the presence of at least one heptamer of chalcane units.

Three new flavans in dragon's blood from Daemonorops draco.

Three new flavans were isolated from chloroform extracts of dragon's blood from Daemonorops draco, together with eight known compounds. The structures of the new flavans were determined by 1D and 2D NMR spectroscopic analysis. These compounds are the first examples of 2-methoxyflavans from D. draco and regarded as derivatives of biogenetic intermediates from flavans to chalcones, which are characteristic of the dragon's blood.

Steroidal saponins from the roots of Asparagus cochinchinensis.

AIM: To study the chemical constituents of the roots of Asparagus cochinchinensis (Asparagaceae). METHODS: The compounds were isolated with Diaion HP20, silica gel, and ODS chromatography, and their structures were determined on the basis of chemical methods, HR-ESI-MS, and 1D- and 2D-NMR techniques. RESULTS: Seven compounds were isolated from the n-butanol fraction of the roots of A. cochinchinensis, and their structures were elucidated as (25S)-26-O-ß-D-glucopyranosyl-5ß-furostan-3ß, 22α, 26-triol-12-one-3-O-ß-D-glucopyranoside (1), (25S)-26-O-ß-D-glucopyranosyl-22α-methoxy-5ß-furostan-3ß, 26-diol-12-one-3-O-ß-D-glucopyranoside (2), (25S)-26-O-ß-D-glucopyranosyl-5ß-furostan-3ß, 22α, 26-triol (3), (25S)-26-O-ß-D-glucopyranosyl-5ß-furstan-3ß, 22α, 26-triol-3-O-ß-D-glucopyranoside (4), (25S)-26-O-ß-D-glucopyranosyl-5ß-furostan-3ß, 22α, 26-triol-3-O-α-L-rhamnopyranosyl-(1, 4)-ß-D-glucopyranoside (5), (25S)-5ß-spirostan-3ß-ol-3-O-α-L-rhamnopyranoside (6), and (25S)-5ß-spirostan-3ß-ol-3-O-ß-D-glucopyranoside (7). CONCLUSION: Compounds 1 and 2 were two new furostanol saponins.