This paper presented how to establish a clinically relevant specification (CRS) using in silico physiologically based pharmacokinetic (PBPK) modeling. Three different formulations of model drug products were used in the clinical studies in order to distinguish between bioequivalent (BE) batches from non-BE batches. A human PBPK model was constructed by integrating the clinical and non-clinical observations by using GastroPlusTM software. The developed model was verified by the comparison between human PK behavior observed in clinical studies and human PK behavior predicted from the software. The simulation results were obtained by using the dissolution profiles showing clinically relevant discriminatory power as input variables for the developed PBPK model. For three investigated formulations, the simulated PK behavior was comparable to the PK behavior observed in clinical studies. In addition, in silico BE simulation studies confirmed that the verified PBPK model can successfully reproduce the clinical study results. In conclusion, a CRS was established with the BE simulation by using the verified PBPK model, in order to detect and reject non-BE batches of drug products. The establishment of the CRS is useful for a quality control and finding optimal formulation to accomplish target PK behavior, safety, and efficacy. V.Maternal obesity programs liver derangements similar to those of NAFLD. Our main goal was to evaluate whether these liver anomalies were related to aberrant PPARα function. Obesity was induced in female Albino-Wistar rats by a fatty diet (FD rats). Several parameters related to NAFLD were evaluated in both plasma and livers from fetuses of 21 days of gestation and 140-day-old offspring. FD fetuses and offspring developed increased levels of AST and ALT, signs of inflammation and oxidative and nitrative stress-related damage. FD offspring showed dysregulation of Plin2, CD36, Cyp4A, Aco, Cpt-1, Hadha and Acaa2 mRNA levels, genes involved in lipid metabolism and no catabolic effect of the PPARα agonist clofibrate. These results suggest that the FD offspring is prone to develop fatty liver, a susceptibility that can be linked to PPARα dysfunction, and that this could in turn be related to the liver impairments programmed by maternal obesity. V.ETHNOPHARMACOLOGICAL RELEVANCE Xuefu Zhuyu decoction (XFZYD) is a traditional Chinese herbal prescription. It is effective in treating traumatic brain injury (TBI). However, the underlying molecular mechanisms remain unclear. AIM OF THE STUDY This study aimed to reveal the possible mechanisms of XFZYD in treating acute TBI through proteomic clues. MATERIALS AND METHODS Controlled Cortical Impact (CCI) rats were gavaged with XFZYD (9 g/kg/d) or distilled water (equal volume) for three days. The Modified Neurological Severity Score (mNSS), brain water content, HE staining, Nissl staining and immunohistochemistry were performed to assess the effects of XFZYD in treating TBI. Additionally, Tandem mass tag-based (TMT) quantitative proteomics technology was applied to detect proteins of the extracted brain cortex. Bioinformatics analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Protein-protein interaction (PPI) networks were used to analysis differentially expressed proteins (DEPs). Bioinformatics Analysis Tool for Molecular mechanism of TCM (BATMAN-TCM) was applied to anchore diseases and pathways of XFZYD. Besides, western blotting and immunofluorescence were used to verify related proteins. RESULTS XFZYD improved neurologic function, reduced encephaledema and ameliorated cell morphology around the injured area in CCI rats. A total of 6099 proteins were identified with FDR (false discovery rate)  less then  1%. 105 overlapping DEPs were identified (295 DEPs and 804 DEPs in CCI/Sham or XFZYD/CCI group respectively). Of these DEPs, 17 were regulated by XFZYD. Bioinformatics analysis showed the 17 DEPs were predominantly related to platelet activation and PI3K-Akt signaling pathway. PLG and CD34 were verified with molecular biotechnology. CONCLUSIONS Our study suggests that XFZYD may exert therapeutic effects through multi-pathways regulation in the treatment of TBI. This work may provide proteomics clues for the continuation researches on XFZYD in treating TBI. V.ETHNOPHARMACOLOGICAL RELEVANCE Litsea cubeba (Lour.) Pers.  https://www.selleckchem.com/products/sb297006.html  has been traditionally used as a folk prescription for treating rheumatic diseases in China. AIM OF THE STUDY This study aimed to investigate the effects and underlying mechanism of LCA, a new type of dibenzyl butane lignin compound extracted from L. cubeba, on macrophage colony stimulating factor (M-CSF) plus receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in mouse-derived bone marrow macrophages (BMMs). MATERIAL AND METHODS TRAP staining, TRAP enzyme activity assay and actin ring staining were applied to identify the effects of LCA on osteoclast differentiation. Protein expression of NFATc1, c-Fos and MMP-9, and phosphorylation of p65, Akt, JNK, ERK and p38 in RANKL-induced osteoclasts was determined using western blotting to investigate the underlying mechanism. RESULTS LCA significantly suppressed RANKL-induced osteoclast differentiation by inhibiting TRAP activity, decreasing the number of TRAP+ multinuclear osteoclasts and reducing the formation of F-actin ring without obvious cytotoxicity in BMMs. Moreover, LCA treatment strongly reduced protein expression of NFATc1, c-Fos and MMP-9, and attenuated the phosphorylation of p65, Akt, JNK, ERK and p38 in RANKL-stimulated BMMs. CONCLUSIONS LCA ameliorated RANKL-induced osteoclast differentiation via inhibition of Akt and MAPK signalings in BMMs, and may serve as a potential pro-drug for bone destruction prevention. V.Callicarpa kwangtungensis, as a characteristic traditional herb in China, has been widely used as indigenous medicine for thousands of years in the treatment of gynecological inflammatory disease in China. Phenylethanoid glycosides (PhGs), as natural polyphenols, are especially abundant in this herb and can be regarded as the representative active ingredients in C. kwangtungensis. This study was performed to investigate the anti-inflammatory pharmacodynamic basis of six PhGs (acteoside, forsythoside B, poliumoside, alyssonoside, Parvifloroside A, and syringalide A 3'-α-L-rhanmnopyranoside) isolated from C. kwangtungensis from the perspective of antioxidation. Compared with the model group, six PhGs revealed obviously inhibitory effects on inflammatory factors TNF-α, IL-6, NO and the generation of ROS in RAW 264.7 macrophages. Further, the effective anti-inflammatory mechanism of two PhGs (forsythoside B and alyssonoside) via Keap1/Nrf2/OH-1 signaling pathway was explored. The experiments confirmed forsythoside B and alyssonoside could act as the inhibitors of Keap1-Nrf2 interaction, then activated the nuclear translocation of Nrf2 and promoted the upregulated protein expression of heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1), finally suppressed LPS-induced inflammatory response in RAW 264.