Gynostemma pentaphyllum (Thunb.) Makino (GpM) (Jiaogulan) has been widely used in Chinese medicine for the treatment of several diseases, including hepatitis, diabetes and cardiovascular disease. Furthermore, GpM has recently been shown to exhibit potent anti-cancer activities. In this review, we have summarized recent research progress on the anti-cancer activities and mechanisms of action of GpM, as well as determining the material basis for the anti-cancer effects of GpM by searching the PubMed, Web of Science and China National Knowledge Infrastructure databases. The content of this review is based on studies reported in the literature pertaining to the chemical components or anti-cancer effects of GpM up until the beginning of August, 2016. This search of the literature revealed that more than 230 compounds have been isolated from GpM, and that most of these compounds (189) were saponins, which are also known as gypenosides. All of the remaining compounds were classified as sterols, flavonoids or polysaccharides. Various extracts and fractions of GpM, as well as numerous pure compounds isolated from this herb exhibited inhibitory activity towards the proliferation of cancer cells in vitro and in vivo. Furthermore, the results of several clinical studies have shown that GpM formula could have potential curative effects on cancer. Multiple mechanisms of action have been proposed regarding the anti-cancer activities of GpM, including cell cycle arrest, apoptosis, inhibition of invasion and metastasis, inhibition of glycolysis and immunomodulating activities.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking targeted therapy currently. Recent studies imply that protein kinase C may play important roles in TNBC development and could be a specific target. In this study, we evaluated the anti-proliferative activity of PKC inhibitor chelerythrine on a panel of breast cancer cell lines. Chelerythrine selectively inhibited the growth of TNBC cell lines compared to non-TNBC cell lines as demonstrated by in vitro cell proliferation assay and colony formation assay, as well as evidenced by in vivo xenograft assay. The selective anti-proliferative effect of chelerythrine was associated with induction of apoptosis in TNBC cell lines. We further demonstrated that PKN2, one of the PKC subtypes, was highly expressed in TNBC cell lines, and knocking down PKN2 in TNBC cells inhibited colony formation and xenograft growth. This indicates that PKN2 is required for the survival of TNBC cells, and could be the target mediates the selective activity of chelerythrine. Finally, combination of chelerythrine and chemotherapy reagent taxol showed synergistic/additive effect on TNBC cell lines. Our results suggest chelerythrine or other PKC inhibitors may be promising regimens for TNBC tumors.

Salvia miltiorrhiza is commonly used as a Chinese herbal medicine to treat different cardiovascular and cerebrovascular illnesses due to its active ingredients. Environmental conditions, especially drought stress, can affect the yield and quality of S. miltiorrhiza. However, moderate drought stress could improve the quality of S. miltiorrhiza without significantly reducing the yield, and the mechanism of this initial drought resistance is still unclear. In our study, transcriptome and metabolome analyses of S. miltiorrhiza under different drought treatment groups (CK, A, B, and C groups) were conducted to reveal the basis for its drought tolerance. We discovered that the leaves of S. miltiorrhiza under different drought treatment groups had no obvious shrinkage, and the malondialdehyde (MDA) contents as well as superoxide dismutase (SOD) and peroxidase (POD) activities dramatically increased, indicating that our drought treatment methods were moderate, and the leaves of S. miltiorrhiza began to initiate drought resistance. The morphology of root tissue had no significant change under different drought treatment groups, and the contents of four tanshinones significantly enhanced. In all, 5213, 6611, and 5241 differentially expressed genes (DEGs) were shared in the A, B, and C groups compared with the CK group, respectively. The results of KEGG and co-expression analysis showed that the DEGs involved in plant-pathogen interactions, the MAPK signaling pathway, phenylpropanoid biosynthesis, flavonoid biosynthesis, and plant hormone signal transduction responded to drought stress and were strongly correlated with tanshinone biosynthesis. Furthermore, the results of metabolism analysis indicated that 67, 72, and 92 differentially accumulated metabolites (DAMs), including fumarate, ferulic acid, xanthohumol, and phytocassanes, which were primarily involved in phenylpropanoid biosynthesis, flavonoid biosynthesis, and diterpenoid biosynthesis pathways, were detected in these groups. These discoveries provide valuable information on the molecular mechanisms by which S. miltiorrhiza responds to drought stress and will facilitate the development of drought-resistant and high-quality S. miltiorrhiza production.