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Parkinson's disease (PD) is the second most common neurodegenerative disease, but none of the current treatments for PD can halt the progress of the disease due to the limited understanding of the pathogenesis. In PD development, the communication between the brain and the gastrointestinal system influenced by gut microbiota is known as microbiota-gut-brain axis. However, the explicit mechanisms of microbiota dysbiosis in PD development have not been well elucidated yet. FLZ, a novel squamosamide derivative, has been proved to be effective in many PD models and is undergoing the phase I clinical trial to treat PD in China. Moreover, our previous pharmacokinetic study revealed that gut microbiota could regulate the absorption of FLZ in vivo . The aims of our study were to assess the protective effects of FLZ treatment on PD and to further explore the underlying microbiota-related mechanisms of PD by using FLZ as a tool. In the current study, chronic oral administration of rotenone was utilized to induce a mouse model to mimic the pathological process of PD. Here we revealed that FLZ treatment alleviated gastrointestinal dysfunctions, motor symptoms, and dopaminergic neuron death in rotenone-challenged mice. 16S rRNA sequencing found that PD-related microbiota alterations induced by rotenone were reversed by FLZ treatment. Remarkably, FLZ administration attenuated intestinal inflammation and gut barrier destruction, which subsequently inhibited systemic inflammation. Eventually, FLZ treatment restored blood-brain barrier structure and suppressed neuroinflammation by inhibiting the activation of astrocytes and microglia in the substantia nigra (SN). Further mechanistic research demonstrated that FLZ treatment suppressed the TLR4/MyD88/NF- κ B pathway both in the SN and colon. Collectively, FLZ treatment ameliorates microbiota dysbiosis to protect the PD model via inhibiting TLR4 pathway, which contributes to one of the underlying mechanisms beneath its neuroprotective effects. Our research also supports the importance of microbiota-gut-brain axis in PD pathogenesis, suggesting its potential role as a novel therapeutic target for PD treatment., Competing Interests: All authors declare no competing interests., (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory infiltration and demyelination in the central nervous system (CNS). Among the factors involved in the immunological mechanisms of MS, T helper 1 (Th1) cells and T helper 17 (Th17) cells play a critical role. Compound 21, a novel phloroglucinol derivative, significantly protected myelin from damage in our previous study. However, it remains unclear whether this compound affects MS. In this study, the experimental autoimmune encephalomyelitis (EAE) rat model was established to mimic the pathological process of MS and evaluate the neuroprotective effect of Compound 21. The results illustrated that Compound 21 treatment notably attenuates neurological deficits, immune infiltration, and demyelination in EAE rats. Our mechanistic investigation revealed that Compound 21 treatment reduces the population of Th1/Th17 cells and inhibits their infiltration into the CNS. Furthermore, we found that the inhibition of Th1/Th17 cell infiltration is related to the direct suppression of Th1/Th17 cell differentiation and the inhibition of proinflammatory microglial cells. Collectively, these results confirm that Compound 21 suppresses infiltrated Th1/Th17 cells to alleviate demyelination in EAE rats, suggesting its potential role as a novel candidate for MS treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ten undescribed highly oxidized sesquiterpenes and six known sesquiterpenes were isolated from H 2 O-soluble part of the fruits of Illicium lanceolatum A. C. Smith. The structures of undescribed compounds were elucidated by interpretation of spectroscopic data, and the absolute configurations of 2α-hydroxyneoanisatinic acid, (1R,5R,6S,7R,9R,10R)-3,4-dehydro-12-hydroxy-floridanolide, and (1R,4S,5R,6S,7S,9S)-1-deoxy-13-hydroxymerrilactone B were determined by the single-crystal X-ray diffraction analysis. Illilanceolatin A was the first example of a seco-prezizaane type sesquiterpene with a hemiacetal moiety located at C-10. 2α-Hydroxyneoanisatinic acid and anisatinic acid were two naturally occurring undescribed seco-prezizaane type sesquiterpenes with a 5/5/6 tricyclic carbon skeleton. Plausible biosynthetic pathways of the isolated polycyclic and highly oxidized sesquiterpenes derived from the intermediate allo-cedrane were proposed. (1R,5R,6S,7R,9R,10R)-3,4-dehydro-12-hydroxy-floridanolide, 1,3-dihydroxyneoanisatin, and 2α-hydroxyneoanisatin displayed neuroprotective effects with protection rates of 19.9, 22.7 and 24.3% at 10 μM, respectively. Additionally, the preliminary acute toxicity of anisatinic acid was also evaluated., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Five new compounds (1-5), including three hexalactone derivatives (1-3) and a pair of new oxaspiro-carbon epimeric glycosides (4 and 5), and six known compounds (6-11) were obtained from the fruits of Illicium lanceolatum. The structures of the new compounds were elucidated using extensive spectroscopic data. The absolute configurations of compounds 1-3 were determined by an analysis of their CD spectra. It was determined that compounds 4 and 5, which are epimeric at C-5, possess the same 1-oxaspiro[4,5]decane-7α,8α,9β-triol moiety. Plausible biogenetic pathways for 4 and 5 derived from the key precursor shikimic acid were proposed. Compounds 1-11 were all assayed on monosodium glutamate-induced human neuroblastoma SH-SY5Y cell damage. The results demonstrated that compounds 4, 5, and 8-10 possess potential neuroprotective effects. The anti-inflammatory, antiviral, and cytotoxic activities of 1-11 were also evaluated., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Three new lupane-type triterpenoids (1-3), three new oleane-type triterpenoids (4-6), as well as two known compounds (7-8) were isolated from Euonymus carnosus. The structures of the compounds were elucidated on the basis of spectroscopic data analyses, including UV, IR, MS, and NMR experiments. The inhibitory on LPS-induced NO production in microglia BV2 cells of compounds 1-8 were also evaluated. Compounds 1 and 2 showed moderate abilities to inhibit NO production, with IC 50 values of 5.99 and 8.47μM, respectively., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Seven new carbazole alkaloids, claulansines L-R (1-7), and six known analogues (8-13) were isolated from the stems of Clausena lansium. Their structures were elucidated on the basis of spectroscopic analyses, including UV, IR, and NMR experiments (HSQC, HMBC, and NOE experiment). Compound 7 showed moderate anti-inflammatory activities. Compounds 3, 5, 6, 8, and 12 exhibited moderate hepatoprotective activities., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Heat shock proteins (HSPs) are the best-known endogenous factors that protect against cell injury under various pathological conditions and that can be induced by various physical, chemical, and biological stressors. New research seeks to discover a compound that is clinically safe and can induce the accumulation of HSPs in patients. This paper reports that the oral administration of three doses of bicyclol, a novel antihepatitis drug, induced hepatic HSP27 and HSP70 expression in a time- and dose-dependent manner, and that bicyclol treatment stimulated heat shock factor 1 (HSF1) activation in mice. The inducing effects of bicyclol on HSP27, HSP70 and HSF1 were all blocked by quercetin, an inhibitor of HSP biosynthesis. The cytoprotective effect of HSP27/70 induced by bicyclol against hepatotoxicity of acetaminophen (AP) was assessed in mice. The prior administration of bicyclol markedly suppressed AP-induced liver injury as indicated by the reduction in the elevation of serum alanine aminotransferase and aspartate aminotransferase, in liver necrosis, in the release of cytochrome c and apoptosis-inducing factor from mitochondria, as well as in hepatic deoxyribonucleic acid fragmentation in mice. However, all the above actions of bicyclol against AP-induced mouse liver injuries were significantly attenuated by quercetin. This is the first report to show that bicyclol induces hepatic HSP27/70 expression via activation of HSF1 and that the cytoprotective action of bicyclol against liver injury is mediated by its induction of HSP27/70. These results provide new evidence for elucidating the mechanism of the hepatoprotective action of bicyclol in animals and patients.