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The figwort genus <i>Scrophularia</i> L. (Scrophulariaceae) comprises 200-300 species and is widespread throughout the temperate Northern Hemisphere. Due to reticulate evolution resulting from hybridization and polyploidization, the taxonomy and phylogeny of <i>Scrophularia</i> is notoriously challenging. Here we report the complete chloroplast (cp) genome sequences of <i>S. henryi</i> Hemsl. and <i>S. dentata</i> Royle ex Benth. and compare them with those of <i>S. takesimensis</i> Nakai and <i>S. buergeriana</i> Miq. The <i>Scrophularia</i> cp genomes ranged from 152 425 to 153 631 bp in length. Each cp genome contained 113 unigenes, consisting of 78 protein-coding genes, 31 transfer RNA genes, and 4 ribosomal RNA genes. Gene order, gene content, AT content and IR/SC boundary structure were nearly identical among them. Nine cpDNA markers (<i>trnH-psbA</i>, <i>rps15</i>, <i>rps18-rpl20</i>, <i>rpl32-trnL</i>, <i>trnS-trnG</i>, <i>ycf15-trnL</i>, <i>rps4-trnT</i>, <i>ndhF-rpl32</i>, and <i>rps16-trnQ</i>) with more than 2% variable sites were identified. Our phylogenetic analyses including 55 genera from Lamiales strongly supported a sister relationship between ((Bignoniaceae + Verbenaceae) + Pedaliaceae) and (Acanthaceae + Lentibulariaceae). Within Scrophulariaceae, a topology of (<i>S. dentata</i> + (<i>S. takesimensis</i> + (<i>S. buergeriana</i> + <i>S. henryi</i>))) was strongly supported. The crown age of Lamiales was estimated to be 85.1 Ma (95% highest posterior density, 70.6-99.8 Ma). The higher core Lamiales originated at 65.6 Ma (95% highest posterior density, 51.4-79.4 Ma), with a subsequent radiation that occurred in the Paleocene (between 55.4 and 62.3 Ma) and gave birth to the diversified families. Our study provides a robust phylogeny and a temporal framework for further investigation of the evolution of Lamiales.
Zuotai is composed mainly of β-HgS, while cinnabar mainly contains α-HgS. Both forms of HgS are used in traditional medicines and their safety is of concern. This study aimed to compare the hepatotoxicity potential of Zuotai and α-HgS with mercury chloride (HgCl2) and methylmercury (MeHg) in mice. Mice were orally administrated with Zuotai (30 mg/kg), α-HgS (HgS, 30 mg/kg), HgCl2 (33.6 mg/kg), or CH3HgCl (3.1 mg/kg) for 7 days, and liver injury and gene expressions related to toxicity, inflammation and Nrf2 were examined. Animal body weights were decreased by HgCl2 and to a less extent by MeHg. HgCl2 and MeHg produced spotted hepatocyte swelling and inflammation, while such lesions are mild in Zuotai and HgS-treated mice. Liver Hg contents reached 45-70 ng/mg in HgCl2 and MeHg groups; but only 1-2 ng/mg in Zuotai and HgS groups. HgCl2 and MeHg increased the expression of liver injury biomarker genes metallothionein-1 (MT-1) and heme oxygenase-1 (HO-1); the inflammation biomarkers early growth response gene (Egr1), glutathione S-transferase (Gst-mu), chemokine (mKC) and microphage inflammatory protein (MIP-2), while these changes were insignificant in Zuotai and HgS groups. However, all mercury compounds were able to increase the Nrf2 pathway genesNAD(P)H: quinone oxidoreductase 1 (Nqo1) and Glutamate-cysteine ligase, catalytic subunit (Gclc). In conclusion, the Tibetan medicine Zuotai and HgS are less hepatotoxic than HgCl2 and MeHg, and differ from HgCl2 and MeHg in hepatic Hg accumulation and toxicological responses.