1.Few studies describing the pharmacokinetic properties of chlorogenic acid (CA) and corydaline (CRD) which are marker compounds of a new prokinetic botanical agent, DA-9701, have been reported. The aim of the present study is to evaluate the pharmacokinetic properties CA and CRD following intravenous and oral administration of pure CA (1-8 mg/kg) or CRD (1.1-4.5 mg/kg) and their equivalent dose of DA-9701 to rats. 2.  Dose-proportional AUC and dose-independent clearance (10.3-12.1 ml/min/kg) of CA were observed following its administration. Oral administration of CA as DA-9701 did not influence the oral pharmacokinetic parameters of CA. Incomplete absorption of CA, its decomposition in the gastrointestinal tract, and/or pre-systemic metabolism resulted in extremely low oral bioavailability (F) of CA (0.478-0.899%). 3.  CRD showed greater dose-normalized AUC in the higher dose group than that in lower dose group(s) after its administration due to saturation of its metabolism via decreased non-renal clearance (by 51.3%) and first-pass extraction. As a result, the F of CRD following 4.5 mg/kg oral CRD (21.1%) was considerably greater than those of the lower dose groups (9.10 and 13.8%). However, oral administration of CRD as DA-9701 showed linear pharmacokinetics as a result of increased AUC and F in lower-dose groups (by 182% and 78.5%, respectively) compared to those of pure CRD. The greater oral AUC of CRD for DA-9701 than for pure CRD could be due to decreased hepatic and/or GI first-pass extraction of CRD by other components in DA-9701.

BackgroundAdiponectin greatly stimulated the expression of matrix metalloproteinases (MMPs) in fibroblast-like synoviocytes (FLSs) as did IL-1β. We wondered whether taurine chloramine (TauCl) inhibits the production of MMPs stimulated by adiponectin in the same pattern as by IL-1β stimulation in vitroMethodsSynovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin or interleukin (IL)-1β for 24 hr in the presence or absence of TauCl. The culture supernatant was collected and the levels of MMPs were measured by enzyme-linked immunosorbent assay (ELISA). The IκB signaling pathways stimulated by adiponectin were studied and the levels of NF-κB in the nuclei of the cells were analyzed by ELISA.ResultsTauCl (600 µM) inhibited MMP-13, but not MMP-1, expression in IL-1β-stimulated RA FLSs. However, TauCl at the same concentration significantly inhibited the production of both adiponectin-stimulated MMP-1 and MMP-13 expression. TauCl inhibited the degradation of IκB-α stimulated by adiponectin, but not by IL-1β. Similarly, the level of NF-κB in the nucleus was increased by adiponectin stimulation and was inhibited by 600 µM TauCl. However, the levels of NF-κB increased by IL-1β stimulation were not inhibited by 600 µM TauCl.ConclusionsTauCl more effectively inhibited MMPs expression induced by adiponectin than that by IL-1β in RA FLS, suggesting that TauCl plays an important role in down-regulating the expression of MMPs in arthritic joints.

Moutan cortex, Angelica Dahurica root, and Bupleurum root are traditional herbal medicines used in Asian countries to treat various diseases caused by oxidative stress or inflammation. Parkinson’s disease (PD) has been associated with mitochondrial dysfunction, but no effective treatment for mitochondrial dysfunction has yet been identified. In this study we investigated the neuroprotective effects of the triple herbal extract DA-9805 in experimental models of PD. DA-9805 was prepared by extracting three dried plant materials (Moutan cortex, Angelica Dahurica root, and Bupleurum root in a 1:1:1 mixture) with 90% ethanol on a stirring plate for 24 h at room temperature and fingerprinted using high-performance liquid chromatography. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridinium (MPP+), which both exert neurotoxic effects on dopaminergic neurons by inhibiting mitochondrial oxidative phosphorylation (OXPHOS) complex I, were used to make experimental models of PD. In MPP+-treated SH-SY5Y cells, DA-9805 ameliorated the suppression of tyrosine hydroxylase expression and mitochondrial damage on OXPHOS complex 1 activity, mitochondrial membrane potential, reactive oxygen species (ROS) generation, and oxygen consumption rate. In the MPTP-induced subacute PD model mice, oral administration of DA-9805 recovered dopamine content as well as bradykinesia, as determined by the rotarod test. DA-9805 protected against neuronal damage in the substantia nigra pars compacta (SNpc) and striatum. In both in vitro and in vivo models of PD, DA-9805 normalized the phosphorylation of AKT at S473 and T308 on the insulin signaling pathway and the expression of mitochondria-related genes. These results demonstrate that the triple herbal extract DA-9805 showed neuroprotective effects via alleviating mitochondria damage in experimental models of PD. We propose that DA-9805 may be a suitable candidate for disease-modifying therapeutics for PD.

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