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The present study investigated whether Jakyak-Gamcho-Tang (JGT, Shaoyao-Gancao-tang) and its constituents have the protective effect against tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity on hippocampal HT22 cell line. JGT consists of two medicinal herbs, Paeoniae Radix (PR) and Glycyrrhizae Radix (GR). In contrast to treating with t-BHP alone, pre-treatment of HT22 cells with JGT, PR and GR (50–400 μg/ml) for 3 hours significantly increased the cell viability in a concentration-dependent manner. In addition, JGT, PR and GR exhibited the scavenging activity in both 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and superoxide anion assays. Among the tested extracts, PR showed the most potent protective and antioxidative activities. These results suggest that PR acts as an antioxidant and this property may contribute to the neuroprotective activity of JGT extract.

Wen-Pi-Tang, an Oriental medical prescription composed of Rhei Rhizoma, Ginseng Radix, Aconiti Tuber, Zingiberis Rhizoma and Glycyrrhizae Radix, is used clinically as a medicine to treat renal failure. This study was conducted to examine the inhibitory activity of the five crude drug components of Wen-Pi-Tang and several pure compounds isolated from Rhei Rhizoma and Glycyrrhizae Radix against the protein glycation reaction. Rhei Rhizoma exerted the most potent activity, Zingiberis Rhizoma and Glycyrrhizae Radix showed relatively moderate activity, whereas Aconiti Tuber and Ginseng Radix showed weak activity. On the other hand, of 20 compounds obtained from Rhei Rhizoma and Glycyrrhizae Radix, tannins, especially rhatannin, RG-tannin and procyanidin B-2 3,3′-di-O-gallate, showed significantly strong activities that were more effective than the positive control, aminoguanidine. Some flavones such as licochalcone A and licochalcone B, and anthraquinones such as emodin and aloe-emodin, also showed inhibitory activity. These findings may help to explain, at least in part, certain pharmacological activities of Wen-Pi-Tang, whose clinical efficacy against renal failure is already recognized.

Oxidative stress plays a key role in the pathophysiologic process of acute and chronic renal diseases. Intracellular component such as lipids, proteins and nucleic acids are easily and rapidly oxidized by excessive reactive oxygen species (ROS), and such reactions lead to increased levels of lipid peroxide. The present study examined the antioxidant effects of Wen-Pi-Tang and its component crude drugs on 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)- or 2,2′-azobis(2,4-dimethylvaleronitrile) (AMVN)-induced ROS generation and lipid peroxidation of linoleic acid. As a result, Wen-Pi-Tang significantly decreased AAPH or AMVN-induced ROS in renal mitochondrial particles. For the components in Wen-Pi-Tang's prescription, Rhei Rhizoma and Glycyrrhizae Radix extracts strongly inhibited peroxide levels, but Ginseng Radix, Aconiti Tuber and Zingiberis Rhizoma extracts were comparably low. Rhei Rhizoma extract showed the strongest inhibitory activity on oxidative injury, and two of its tannin compounds, (-)-epicatechin 3-O-gallate and procyanidin B-2 3,3′-di-O-gallate, inhibited AAPH or AMVN-induced ROS significantly. Thus, the present data suggest that Wen-Pi-Tang and its component crude drugs effectively prevent biological toxicity on oxidative stress through potent antioxidant and anti-lipid peroxidation activities.

Osteoporosis results from imbalance between new bone formation and bone resorption leading to bone loss and is especially troublesome for postmenopausal women who suffer from estrogen deficiency. The ability of new therapeutic agents to treat this bone disease with minimal side effects has been extensively reported on and is continuously being sought out by researchers in this field. Thus, the purpose of this study was to investigate a natural herb that was already being used as a new treatment for osteoporosis. Here we found that water extract of Glycyrrhizae radix (GR) inhibits receptor activator of nuclear factor-$\kappa$B ligand (RANKL)-induced osteoclast differentiation in a dose-dependent manner without causing cytotoxicity. The mRNA expression of c-Fos, nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and osteoclast-associated receptor (OSCAR) was considerably inhibited by GR treatment. GR inhibited RANKL-mediated c-Fos and NFATc1 expression in a dose-dependent manner. GR inhibited the degradation of I-$\kappa$B in RANKL-stimulated BMMs. However, GR-mediated inhibition of osteoclast differentiation and osteoclast-specific gene expression, including NFATc1, was reversed by ectopic expression of c-Fos. Also, GR significantly inhibited osteoclast formation in mouse calvariae in the presence of IL-1 and prostaglandin E2 (PGE2). Taken together, these results suggest that GR inhibited osteoclast differentiation, raising the possibility that GR may serve as a useful drug for osteoporosis.