Pepper is one of the most popular spices over the world and is called the King of Spices. Its essential oils (EOs) could alleviate neuronal ailments due to the inhibitory effect against acetylcholinesterase (AChE). In this study, the chemical compositions of 26 EOs prepared from white and black pepper collecting from 6 different cultivars were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 133 compounds were identified in the white and black pepper EOs. Monoterpenes and sesquiterpenes were found to be riched in these EOs, of which α-pinene, β-pinene, sabinene, 3-carene, limonene, and ( E)- β-caryophyllene were the major constituents. Most of pepper EOs showed potential AChE inhibitory activity with half-maximal inhibitory concentration (IC50) values in the range of 0.5-182.5 µg/mL. Comparison of chemical constitutes of pepper EOs from different cultivars suggested that α-pinene, β-pinene, and 3-carene with an IC50 value of 3.2, 53.3, and 2.9 µg/mL, respectively, might be used as Quality-marker (Q-marker) of pepper oil in inhibiting AChE.

The chemical compositions of essential oils (EOs) prepared from six spices including cinnamon, amomum tsao-ko, cardamom, amomum, black pepper and white pepper were analyzed by gas chromatography-mass spectrometry (GC/MS), which led to identify almost 200 volatile compounds. All EOs of spices showed cholinesterase inhibitory activity. Among them, pepper EO showed most potent acetylcholinesterase (AChE) inhibitory activity with IC 50 values of 8.54 μg/mL (black pepper EO) and 5.02 μg/mL (white pepper EO). Molecular docking and in vitro validation suggested that 3-carene, α-pinene and β-pinene with IC 50 value of 1.73, 2.66, and 14.75 μg/mL, respectively, might be active constituents of spices oil in inhibiting AChE. Furthermore, amomum tsao-ko EO and amomum EO can improve behavioral disorder in dementia zebrafish induced by aluminum trichloride (AlCl 3 ).

No abstract

Background Voltage gated sodium channels are essential for the generation of exceptional pain signals after peripheral nerve injury. Among them, voltage-gated sodium (Nav) subtype Nav1.7 is a powerful target for a broad range of pain conditions. Maslinic acid, one of the most common pentacyclic triterpenes widely distributed in medicinal plants, showed pharmacologic safety and potent pharmacological action. Herein, we present maslinic acid (MA) as an inhibitor of Nav1.7 with analgesic efficacy in rodent pain models. Methods We first explored the target of maslinic acid using the CMap method and patch clamp recording. Maslin acid and its inactive analogue (oleanolic acid as negative controls) was used to culture MCF-7 cells. Then, we performed RNA-seq of the cultured MCF-7 cells and analyzed the transcriptome data. The differential genes were identified and used as an input for CMap. The CMap result was further confirmed by patch clamp recording. Results The CMap result suggested that maslinic acid was an agonist of Nav channels. Further whole cell patch-clamp experiments revealed that maslinic acid inhibited the Nav1.7 channel with an IC50 value of 6.1 µM. Conclusion Maslinic acid showed a potent analgesic effect in two rodent models of formaldehyde and acid-induced pain. Our findings show novel insights into the new target of maslinic acid in complex neurological disorders. Maslinic acid targeting Nav1.7 is a new analgesic lead.

HBV infection is a major global health burden that needs novel immunotherapeutic approaches. Herein, we show that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a novel drug target for HBV infection. We reveal the new target with highly selective probes of PAC5, a natural sesquiterpene derivative. PAC5 show potent anti-HBV activity in vivo and in vitro. Further studies on its mode of action indicate that PAC5 binds to the residue Asp49 and a deep groove in the RNA recognition motif1 (RRM1) region of hnRNPA2B1. PAC5-bound hnRNPA2B1 is activated, dimerized, and translocated to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to the production of type I interferons (IFNs). Furthermore, PAC5 also suppresses other viral replications, such as SARS-CoV-2 and vesicular stomatitis virus (VSV). Our results indicate that PAC5 is the first small molecule agonist of hnRNPA2B1, a drug target potentially valid for broad-spectrum viral infections, providing a novel strategy for viral immunotherapy.