Effect Of LIG Research Articles

Antidepressant-like effects of Z-ligustilide on chronic unpredictable mild stress-induced depression in rats.

Depression is a significant public health issue and its neuropathogenesis is associated with the dysfunction of progesterone and allopregnanolone biosynthesis. Z-ligustilide (LIG), one of the main components of the herb Angelica sinensis (Oliv.) Diels (AS), is reported to have antidepressant activities. The present study aimed to evaluate the antidepressant-like effects of LIG via behavioral tests and to measure the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus. The results demonstrated that LIG (20 and 40 mg/kg) exerted antidepressant-like effects, confirmed by increased mobility, locomotion, rearing frequency and preference to sucrose. Furthermore, the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus were markedly increased following treatment with LIG (20 and 40 mg/kg), indicating that both neurosteroids could serve a significant role in the antidepressant-like effects of LIG.

Ligustrazine Inhibits Cartilage Endplate Hypertrophy via Suppression of TGF-β1.

CEP hypertrophy is one of the characteristics of intervertebral disc degeneration (IDD). LIG exerts a protective effect on IDD in animal model. The effect of LIG on CEP hypertrophy is further investigated in the present study. Cells were isolated from hypertrophic samples obtained from patients during vertebral fusion surgery. Cellular proliferation and the expression of type I collagen (Col I) and TGF-β1 were tested. In the bipedal rats, the edges of the CEP and the sizes of noncartilaginous outgrowth, as well as the expression of osteogenic markers, Col1a, ALP, Runx2, and TGF-β1, were detected. Within two passages, the condensed hypertrophic CEP cells exhibited osteogenic capacity by bony-like nodules and ALP positive staining, along with increased expression of Col I and TGF-β1. LIG inhibited proliferation of CEP cells and downregulated the expression of Col I and TGF-β1 in vitro. Furthermore, LIG attenuated CEP hypertrophy on the lumbar spine of bipedal rats by reducing Col1a, ALP, Runx2, and TGF-β1 mRNA expression and TGF-β1 distribution in vivo. We concluded LIG exerted a preventive effect on CEP hypertrophy via suppression of TGF-β1 levels. This information could be used to develop alternative therapeutic methods to treat spinal CEP hypertrophy.

Second pathway for completion of human DNA base excision-repair: reconstitution with purified proteins and requirement for DNase IV (FEN1).

Two forms of DNA base excision-repair (BER) have been observed: a 'short-patch' BER pathway involving replacement of one nucleotide and a 'long-patch' BER pathway with gap-filling of several nucleotides. The latter mode of repair has been investigated using human cell-free extracts or purified proteins. Correction of a regular abasic site in DNA mainly involves incorporation of a single nucleotide, whereas repair patches of two to six nucleotides in length were found after repair of a reduced or oxidized abasic site. Human AP endonuclease, DNA polymerase beta and a DNA ligase (either III or I) were sufficient for the repair of a regular AP site. In contrast, the structure-specific nuclease DNase IV (FEN1) was essential for repair of a reduced AP site, which occurred through the long-patch BER pathway. DNase IV was required for cleavage of a reaction intermediate generated by template strand displacement during gap-filling. XPG, a related nuclease, could not substitute for DNase IV. The long-patch BER pathway was largely dependent on DNA polymerase beta in cell extracts, but the reaction could be reconstituted with either DNA polymerase beta or delta. Efficient repair of gamma-ray-induced oxidized AP sites in plasmid DNA also required DNase IV. PCNA could promote the Pol beta-dependent long-patch pathway by stimulation of DNase IV.