[Effects of Xihuang Pills on proliferation and apoptosis of prostate cancer LNCaP cells based on AR/m TOR signaling pathway].

Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.

C21 steroids from the roots of Marsdenia tenacissima.

A phytochemical investigation of the dichloromethane soluble fraction of the ethanolic extract obtained from the roots of Marsdenia tenacissima led to the discovery of the sixteen undescribed pregnane C21 steroids (1-16) and isolation of eleven known C21 steroidal analogues (17-27). Their chemical structures were elucidated by one- and two-dimensional nuclear magnetic resonance spectroscopy and, high resolution-electrospray ionization mass spectrometry and their absolute configurations were determined using electronic circular dichroism or single-crystal X-ray diffraction. The in vitro anti-proliferative effects of 1-16 were evaluated against HepG2 (human hepatocellular cancer), A549 (lung cancer), and MCF-7 (human breast cancer) cell lines. Even though some of them showed moderate cytotoxic activities, marsectohexol derivative 12 exhibited significant cytotoxicity against A549 cells with an IC50 value of 5.2 µM.

Anti-Inflammatory Activities of Monoterpene and Sesquiterpene Glycosides from the Aqueous Extract of Artemisia annua L.

Artemisia annua L. is a Chinese medicinal herb, but the origin of its pharmacological properties, including its anti-inflammatory activity, remain unknown. In this study, five new monoterpene glycosides (1-5) and two new sesquiterpene glycosides (6 and 7) were isolated from the aqueous extract of the aerial parts of A. annua. The structures of these glycosides were determined using high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, electronic circular dichroism calculations, and chemical hydrolysis methods. The anti-inflammatory activities of the isolated compounds were evaluated by down-regulating interleukin-6 (IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Notably, all the new compounds significantly inhibited the expression of IL-6 in a dose-dependent manner.

Comprehensive profiling and characterization of the absorbed components and metabolites in mice serum and tissues following oral administration of Qing-Fei-Pai-Du decoction by UHPLC-Q-Exactive-Orbitrap HRMS.

Qing-Fei-Pai-Du decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery, viral shedding, hospital stay, and course of the disease. However, the effective constituents of QFPDD remain unclear. In this study, an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.

Acylated iridoid glucosides from Pseudocaryopteris paniculata (C.B.Clarke) P.D.Cantino.

Phytochemical investigation of the ethyl acetate fraction of Pseudocaryopteris paniculata C.B.Clarke P.D.Cantino resulted in the identification of 26 undescribed iridoid glucosides (paniculosides A-Z), along with 7 known iridoid glucosides. Their structures were elucidated via two-dimensional nuclear-magnetic-resonance (2D-NMR) spectroscopy, high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS), and chemical-hydrolysis methods. All isolated substances were analyzed for their cytoprotective effects against t-BHP-induced toxicity in HepG2 cells. Among the tested compounds, paniculoside A, paniculoside I, paniculoside T, and paniculoside U exhibited moderate cytoprotective activities with IC50 values in the range of 11.72-34.22 µM against t-BHP-induced toxicity.

Na⁺-K⁺-ATPase, a potent neuroprotective modulator against Alzheimer disease.

Alzheimer disease (AD) is a neurodegenerative disorder clinically characterized by progressive cognitive and memory dysfunction, which is the most common form of dementia. Although the pathogenesis of neuronal injury in AD is not clear, recent evidences suggest that Na⁺-K⁺-ATPase plays an important role in AD, and may be a potent neuroprotective modulator against AD. This review aims to provide readers with an in-depth understanding of Na⁺-K⁺-ATPase in AD through these modulations of some factors that are as follows, which leads to the change of learning and memory in the process of AD. 1. The deficiency in Na⁺, K⁺-ATPase α1, α2 and α3 isoform genes induced learning and memory deficits, and α isoform was evidently changed in AD, revealing that Na⁺, K⁺-ATPase α isoform genes may play an important role in AD. 2. Some factors, such as ß-amyloid, cholinergic and oxidative stress, can modulate learning and memory in AD through the mondulation of Na⁺-K⁺-ATPase activity. 3. Some substances, such as Zn, s-Ethyl cysteine, s-propyl cysteine, citicoline, rivastigmine, Vit E, memantine, tea polyphenol, curcumin, caffeine, Alpinia galanga (L.) fractions, and Bacopa monnieri could play a role in improving memory performance and exert protective effects against AD by increasing expression or activity of Na⁺, K⁺-ATPase.