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[This corrects the article DOI: 10.3389/fphar.2020.01261.].[This corrects the article DOI: 10.3389/fphar.2020.01261.].

The bulb of Fritillaria species called “Bei Mu” is a well-known traditional Chinese medicine. We have reported some potential off-target effects of “Bei Mu” due to peimine’s blockade of hERG (human Ether-a-go-go-Related Gene) channels. This research investigated the modulatory effects of three major alkaloid analogs of “Bei Mu” and their cooperative effects on hERG channels using manual whole-cell patch-clamp techniques. Results showed that peiminine and sipeimine blocked hERG currents with IC50s of 36.8 ± 2.5 μM and 47.6 ± 9.8 μM, which were close to that of peimine (26.1 ± 3.5 μM). Peiminine-induced blockade increased with increasing depolarizing strengths, durations, and frequencies, which suggested a preferential binding to open or inactivated states. The reduced blockade by the less inactivating S631A mutation supported peiminine‘s inactivation preference. Molecular docking and dynamics simulations confirmed the hERG-blocking activities of the three alkaloids and provided further insight into potential mechanisms. We also discovered antagonistic effects of the three alkaloids at nearly all concentrations tested, which might help reduce potential cardiotoxicities. To our knowledge, this is the first study to investigate combination effects of chemicals from one herb on hERG channels. In conclusion, peiminine and sipeimine can block hERG channels in a way similar to peimine, but antagonistic effects exist among them.

The herb Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae family), also known as Tu-Bei-Mu (TBM) in Chinese, has shown curative effects to treat several types of cancer as an adjunctive therapy. Thereby we intend to find its effect on the human hepatocellular carcinoma (HCC) and to understand the pharmacological mechanism behind it. In this study, an integrative serum pharmacology-based approach linking serum pharmacology and bioinformatics prediction was employed. Firstly, we used the serum taken introgastrically from the rats dministered by TBM aqueous bulb extract to culture the HCC cell line BEL-7404 and detect its anti-tumor effects. Secondly, the TBM putative targets were predicted using the ETCM database and known therapeutic targets of NPC were collected from the OMIM database. Then, a TBM-HCC putative targets network was constructed using the DAVID and STRING databases. Thirdly, key gene targets were obtained based on topological analysis and pathway enrichment analysis. The expression of 4 representative key targets were validated by Western blotting. As a result, 36 TBM targets and 26 known therapeutic targets of HCC were identified. These key targets were found to be frequently involved in 13 KEGG pathways and 4 biological processes. The expression of four representative key targets: TP53, CASP3, BCL2 and BAX further supports the suppression of TBM on HCC. In general, our study shows the curative effects of TBM against HCC. By using this integrative approach, we may find novel potential therapeutic targets to suppress HCC using TBM as an adjunctive therapy. And it could also help us understand the mechanism of HCC treatments in response to TBM.

Background Bei Mu Gua Lou San (BMGLS) is an ancient formulation known for its moisturizing and expectorant properties, but the underlying mechanisms remain unknown. We investigated concentration-dependent effects of BMGLS on its rehydrating and mucus-modulating properties using an air-liquid-interface (ALI) cell culture model of the Calu-3 human bronchial epithelial cell line and primary normal human bronchial epithelial cells (NHBE), and specifically focused on quantity and composition of the two major mucosal proteins MUC5AC and MUC5B. Methods ALI cultures were treated with BMGLS at different concentrations over three weeks and evaluated by means of histology, immunostaining and electron microscopy. MUC5AC and MUC5B mRNA levels were assessed and quantified on protein level using an automated image-based approach. Additionally, expression levels of the major mucus-stimulating enzyme 15-lipoxygenase (ALOX15) were evaluated. Results BMGLS induced concentration-dependent morphological changes in NHBE but not Calu-3 ALI cultures that resulted in increased surface area via the formation of herein termed intra-epithelial structures (IES). While cellular rates of proliferation, apoptosis or degeneration remained unaffected, BMGLS caused swelling of mucosal granules, increased the area of secreted mucus, decreased muco-glycoprotein density, and dispensed MUC5AC. Additionally, BMGLS reduced expression levels of MUC5AC, MUC5B and the mucus-stimulating enzyme 15-lipoxygenase (ALOX15). Conclusions Our studies suggest that BMGLS rehydrates airway mucus while stimulating mucus secretion by increasing surface areas and regulating goblet cell differentiation through modulating major mucus-stimulating pathways.

Die Auseinandersetzung mit dem Westen stellt einen der Schwerpunkte im Denken iranischer Intellektueller dar.Mit Muhammad Husayn Tabataba'i (1903-1981) und Murtaza Mutahhari (1920-1979) werden in diesem Buch zwei Vertreter der iranischen Geistesgeschichte des 20.

The Ben cao gang mu, compiled in the second half of the sixteenth century by a team led by the physician Li Shizhen (1518-1593) on the basis of previously published books and contemporary knowledge, is the largest encyclopedia of natural history in a long tradition of Chinese materia medica works. Its description of almost 1,900 pharmaceutically used natural and man-made substances marks the apex of the development of premodern Chinese pharmaceutical knowledge. The Ben cao gang mu dictionary offers access to this impressive work of 1,600,000 characters. This first book in a three-volume series analyzes the meaning of 4,500 historical illness terms.

Are jihadists dying for a fiction? Everything you thought you knew about Islam is about to change. Did Muhammad exist? It is a question that few have thought-or dared-to ask. Virtually everyone, Muslim and non-Muslim alike, takes for granted that the prophet of Islam lived and led in seventh-century Arabia. But this widely accepted story begins to crumble on close examination, as Robert Spencer shows in his eye-opening new book. In his blockbuster bestseller The Truth about Muhammad, Spencer revealed the shocking contents of the earliest Islamic biographical material about the prophet of Islam. Now, in  Did Muhammad Exist? , he uncovers that material's surprisingly shaky historical foundations. Spencer meticulously examines historical records, archaeological findings, and pioneering new scholarship to reconstruct what we can know about Muhammad, the Qur'an, and the early days of Islam. The evidence he presents challenges the most fundamental assumptions about Islam's origins. Did Muhammad Exist?  reveals: *How the earliest biographical material about Muhammad dates from at least 125 years after his reported death*How six decades passed before the Arabian conquerors-or the people they conquered-even mentioned Muhammad, the Qur'an, or Islam*The startling evidence that the Qur'an was constructed from existing materials-including pre-Islamic Christian texts*How even Muslim scholars acknowledge that countless reports of Muhammad's deeds were fabricated*Why a famous mosque inscription may refer not to Muhammad but, astonishingly, to Jesus*How the oldest records referring to a man named Muhammad bear little resemblance to the now-standard Islamic account of the life of the prophet*The many indications that Arabian leaders fashioned Islam for political reasons Far from an anti-Islamic polemic,  Did Muhammad Exist?  is a sober but unflinching look at the origins of one of the world's major religions. While Judaism and Christianity have been subjected to searching historical criticism for more than two centuries, Islam has never received the same treatment on any significant scale. The real story of Muhammad and early Islam has long remained in the shadows. Robert Spencer brings it into the light at long last.