One of the largest concerns with world health today is still antibiotic resistance, which is making it imperative to find efficient alternatives as soon as possible. It has been demonstrated that microbes are reliable sources for the creation of therapeutic antibiotics. This research intends to investigate the endophytic microorganisms from several medicinal plants in Fenghuang Mountain (Jiangsu Province, China) and to discover new antibiotics from their secondary metabolites. A total of 269 endophytic strains were isolated from nine distinct medicinal plants. Taxonomic analysis revealed that there were 20 distinct species among these endophytes, with Streptomyces being the most common genus. Three of the target strains were chosen for scale-up fermentation after preliminary screening of antibacterial activities and the metabolomics investigation using LC-MS. These strains were Penicillium sp. NX-S-6, Streptomyces sp. YHLB-L-2 and Streptomyces sp. ZLBB-S-6. Twenty-three secondary metabolites (1–23), including a new sorbicillin analogue (1), were produced as a result of antibacterial activity-guided isolation. Through spectroscopic analysis using MS and NMR, the structures of yield compounds were clarified. According to antibacterial data, S. aureus or B. subtilis were inhibited to varying degrees by sorrentanone (3), emodic acid (8), GKK1032 B (10), linoleic acid (14), toyocamycin (17) and quinomycin A (21). The most effective antimicrobial agent against S. aureus, B. subtilis, E. coli and A. baumannii was quinomycin A (21). In addition, quinomycin A showed strong antifungal activity against Aspergillus fumigatus, Cryptococcus neoformans, and two clinical isolated strains Aspergillus fumigatus #176 and #339, with MIC as 16, 4, 16 and 16 µg/mL, respectively. This is the first time that bioprospecting of actinobacteria and their secondary metabolites from medicinal plants in Fenghuang Mountain was reported. The finding demonstrates the potential of endophytic microbes in medical plants to produce a variety of natural products. Endophytic microbes will be an important source for new antibiotics.

Licorice is mainly used to treat cough in clinics. After being roasted with honey, licorice has a cardiac protective effect. Due to its different sources, the chemical components in licorice are also diverse. To distinguish the different compounds between three sources of raw licorice (RL) and between three sources of honey-roasted licorice (HRL), a UPLC-QTOF-MS/MS method was established. Eighteen batches of samples were analyzed which were derived from Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat., and Glycyrrhiza glabra L. In addition, the potential key pathways of HRL to anti-arrhythmia were explored by network pharmacology. Among the three sources of RL, 77 differential compounds were detected in the positive ion mode; and 62 differential compounds were detected in the negative ion mode, of which 21 differential compounds were detected in both ion modes. Twenty-nine differential compounds were identified before and after honey-roasted of G. uralensis Fisch., 51 and 17 differential compounds were identified in G. glabra L. and G. inflata Bat., receptively. The network pharmacological analysis predicted that Rap1, Ras, PI3K-Akt, and cAMP signaling pathway might be closely related to the anti-arrhythmia mechanism of HRL. This study provides a theoretical reference for the quality improvement and clinical application of licorice. Graphical Abstract

The “Shang Han Lun” indicates that honey-processed licorice protects the heart better than raw licorice. Ten major constituents in honey-processed licorice samples were quantified. Protective effects of honey-processed licorices against doxorubicin-induced cardiotoxicity were assessed in zebrafish larvae. Network pharmacology analysis based on the ten target constituents was conducted. Results showed glabridin was lowest in honey-processed Gg, while total content of six components (such as liquiritin) was highest in honey-processed Gu, followed by honey-processed Gi, and lowest in honey-processed Gg. Pharmacological results indicated that honey-processed Gu and Gi significantly improved doxorubicin-induced abnormal pericardial edema and increased venous sinus-arterial bulb distance in larvae. The pericardial area was reduced by 23% and 20%, respectively compared to the model group, and the distances reduced to 81% and 83.3% of the model group, respectively. Although improvements in pericardial edema were rare in the honey-processed Gg group, it reversed venous sinus-arterial bulb distance increase. These results indicate that honey-processed Gu and honey-processed Gi can significantly protect zebrafish embryos against the effects of doxorubicin-induced cardiotoxicity, namely, abnormal heart rate, pericardial edema, and elongation of the venous sinus-arterial bulb distance, whereas honey-processed Gg can only significantly reverse the doxorubicin-induced increase in the venous sinus-arterial bulb distance. Network pharmacology analysis predicted that these constituents have potential for the treatment of metabolic abnormalities and cellular senescence related diseases caused by reactive oxygen species induction, linking to Rap1 pathways. Honey-processed Gu and honey-processed Gi had stronger cardioprotective effects on zebrafish embryos than honey-processed Gg possibly because of differences in composition.