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Ethnopharmacological relevance The whole plant of Glycine tabacina (Labill.) Benth has been used as a traditional herbal medicine to treat rheumatism, ostealgia and nephritis in China. It is also one of the sources of the renowned native herbal medicine ‘I-Tiao-Gung’ in Taiwan. Aim of the study This study aimed to investigate the anti-arthritic effect of ethanol extract of G. tabacina (GTE) in a collagen-induced arthritis (CIA) rat model. Materials and methods The chemical profile of GTE was analyzed by HPLC-UV. The CIA was induced in male Wistar rats by intradermal injection of bovine type II collagen at tail root, back and ankle joints. The rats were orally administrated daily with GTE (1.11, 2.22 and 4.44 g dry weight of herb powder per kg body weight) from day 0 and continued for 30 days. Swelling volume and thickness of paw, arthritis index, X-radiographs and histopathological changes were examined to assess the severity of arthritis. Furthermore, the levels of pro-inflammatory cytokines, such as interleukin1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α), total superoxide dismutase (T-SOD) activity and malonaldehyde (MDA) level were measured to preliminarily explore the possible mechanisms. Results Oral administration of GTE significantly ameliorated the arthritic symptoms in CIA rat model, as indicated by the effects on paws swelling and arthritis index. X-radiographic analysis and histopathological examinations demonstrated that GTE effectively protected the bone and cartilage of joints from erosion, lesion and deformation. The efficacy of GTE treatment on CIA was comparable to that of indomethacin (positive drug). Besides, the overproduction of IL-1β, IL-6 and TNF-α was remarkably inhibited in the serum of all GTE treatment groups. The restoration of serum T-SOD activity and MDA level proved that GTE administration alleviated the oxidative stress in CIA rats. Conclusions GTE exhibited strong anti-CIA activity through inhibiting pro-inflammatory cytokines and oxidation in rats, suggesting its potential preventive and therapeutic effects on rheumatoid arthritis (RA).

Background Polysaccharides, one of the active ingredients in herbal medicine, are proved to enhance innate immunity against infections. The aim of this study is to explore the immunoregulatory ability of polysaccharides from Rhynchosia minima root in vitro and in vivo. Methods Polysaccharide fractions of R. minima root were obtained by chromatographic column. The content of NO was measured by spectrophotometry. The levels of cytokines (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6; and monocyte chemoattractant protein-1, MCP-1) were determined by enzyme-linked immuno-sorbent assay (ELISA) kits. The translocation of p65 into the nucleus was imaged by confocal microscopy. The mRNA expression of TNF-α, IL-6, and MCP-1 was determined by quantitative real-time PCR. T-lymphocyte subgroups of spleen from immunosuppressive mouse were evaluated by flow cytometry. Results PRM3 remarkably enhanced the phagocytic ability of macrophages and promoted the release of NO and the secretion of cytokines (TNF-α, IL-6, and MCP-1) from macrophages. Simultaneously, PRM3 potently activated NF-κB signaling pathway via Toll-like receptor 4 (TLR4). In addition, PRM3 obviously increased the levels of serum cytokines, markedly up-regulated the percentages of CD3+ and CD4+ T lymphocytes and the CD4+/CD8+ ratio of splenocytes, and effectively attenuated cyclophosphamide induced immunosuppression in mice. Conclusions PRM3 profoundly enhanced the immune function in vitro and in vivo through TLR4-NF-κB pathway and is a promising candidate of immunopotentiator which could be applied in functional foods or drugs. General significance This study reported a polysaccharide PRM3 from R. minima root exhibited potent immunoenhancing activity and significantly alleviated cyclophosphamide-induced immunosuppression through TLR4-NF-κB pathway.

An herb commonly contains hundreds of constituents. Identification of bioactive compound(s) in each herb using conventional approaches is usually inefficient and eco-unfriendly. In this study, we aimed to fast identify anticancer compounds in Forsythiae Fructus using UPLC/MS-based metabolomics analysis. We firstly fractionated Forsythiae Fructus crude extracts with organic solvents of different polarity, then the chemical profile of each fraction was analyzed by UPLC/Q-TOF/MS, and the anticancer activity profiles of all fractions were determined by MTT assay. Next, orthogonal projections to latent structures discriminant analysis (OPLS-DA) was applied to discriminate fractions with different anticancer activity to determine the compound(s) that contributes most to the anticancer activity. Betulinic acid was then identified to be the most potent anticancer compound in Forsythiae Fructus. Its predicted anticancer activity was confirmed by MTT assay. Taken together, our results demonstrated that the present integrated metabolomics strategy could be used for fast identification of anticancer compound(s) in herb extracts or other complex mixtures of chemicals.

Rhynchosia minima root, a folk herbal medicine in southern China, is used to relieve itch and swelling. In this study, we examined the anti-inflammatory property of an ethanol fraction (EEF6) from R. minima root on lipopolysaccharide (LPS)-induced RAW 264.7 cells, as well as its underlying mechanism. The compound composition of EEF6 was determined by high-performance liquid chromatography-mass spectrometry. The result showed that five flavonoids compounds, 2',4',5,7-tetrahydroxyisoflavone, genistein-8-C-glucopyranoside, tricin, genistein, and daidzein, were identified in EEF6. In addition, EEF6 exhibited potent anti-inflammatory ability against LPS-stimulated RAW 264.7 cells via MAPK/NF-κB signaling pathways by decreasing the secretion of nitric oxide (NO), interleukin (IL)-6, TNF-α, and monocyte chemotactic protein (MCP)-1, inhibiting the translocation of p65 from cytoplasm to nucleus, and suppressing the phosphorylation of ERK, JNK, and p38. These results indicated that EEF6 could be a promising ingredient for inflammation management.

Context: Litsea coreana H. Lév. (Lauraceae) is used as an ethnic herb or beverage in China. Substantial studies indicate that it contains a variety of compounds and shows diverse bioactivities with no toxicity. Objective: This review analyzes and summarizes the ethnopharmacological applications, phytochemistry, and pharmacological activities and molecular mechanisms of L. coreana. Methods: Related literature (from 1998 to 2016) was obtained and compiled via searching databases including Scopus, Web of Science, Google Scholar, CNKI and PubMed. Keywords (Litsea coreana, hawk tea, eagle tea and laoying cha) were used to select the articles. Results: Studies indicate that L. coreana contains characteristic polysaccharides, polyphenols, essential oils, and numerious flavonoids, which exhibit remarkable bioactivities, such as hepatoprotection, hyperglycaemia, anti-inflammation, antioxidation and antibacterial, through multiple molecular mechanisms. Conclusion: This paper provides a systematic review on the phytochemicals and pharmacological activities of L. coreana which should be useful for further study and application of this medicinal herb.

Forsythiae Fructus, Lianqiao in Chinese, is one of the most fundamental herbs in Traditional Chinese Medicine. Both green Forsythia (GF) and ripe Forsythia (RF) are referred to Forsythiae Fructus in medicinal applications. In most cases, they are used without distinction. In this study, a metabolomics approach was performed to compare componential differences of two Forsythiae Fructus aqueous extracts subtypes. Principal component analysis (PCA) score plots from the UPLC-MS data showed clear separation between the two subtypes, indicating there are significant differences in the chemical components between GF and RF. Meanwhile, the anticancer activity of them was also compared. GF exhibited much stronger antitumor activity than RF against B16-F10 murine melanoma both in vitro and in vivo. 15 chemical compounds were identified as specific markers for distinguishing GF and RF. Among these marker compounds, forsythoside I, forsythoside A, forsythoside E and pinoresinol were demonstrated to be key important active compounds that account for the different anticancer efficacies of GF and RF. Our data suggest that GF and RF should be distinctively used in clinical applications, particularly in the anticancer formulas, in which GF should be preferentially prescribed.

Background: Polyphyllin VII (PP7), a steroidal saponin from Paris polyphylla, has been found to exert strong anticancer activity. Little is known about the anti-inflammatory property of PP7. In this study, the anti-inflammatory activity and its underlying mechanisms of PP7 were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in multiple animal models. Methods: The content of nitric oxide (NO) was determined by spectrophotometry. The levels of prostaglandin E2 (PGE2) and cytokines were measured by enzyme-linked immunosorbent assay (ELISA) assay. The mRNA expression of pro-inflammatory genes was determined by qPCR. The total and phosphorylated protein levels were examined by Western blotting. The in vivo anti-inflammatory activities were evaluated by using mouse and zebrafish models. Results: PP7 reduced the production of NO and PGE2 and the protein and mRNA expressions of pro-inflammatory cytokines (TNF-&alpha, IL-1&beta, and IL-6) and enzymes (inducible NO synthase [iNOS], cyclooxygenase-2 [COX-2], and Matrix metalloproteinase-9 [MMP-9]) in LPS-induced RAW264.7 cells by suppressing the NF-&kappa, B and MAPKs pathways. Notably, PP7 markedly inhibited xylene-induced ear edema and cotton pellet-induced granuloma formation in mice and suppressed LPS and CuSO4-induced inflammation and toxicity in zebrafish embryos. Conclusion: This study demonstrates that PP7 exerts strong anti-inflammatory activities in multiple in vitro and in vivo models and suggests that PP7 is a potential novel therapeutic agent for inflammatory diseases.

Pulsatilla saponin D (SB365), a saponin isolated from rhizoma of Pulsatilla chinensis (Bunge) Regel, exhibited anticancer activities in various cancer types. In the present study, we identified that SB365 was a potent inhibitor of autophagic flux in several cancer cell lines. SB365 induced a robust accumulation of autophagosomes as evidenced by monodansylaervarine (MDC) staining and increased protein levels of LC3-II. However, SB365 caused the accumulation of p62, a substrate that should be degraded through the autophagy–lysosomal pathway. These results indicated that SB365 was an inducer of autophagosome formation, but an inhibitor of autophagic flux. Interestingly, we found that SB365 synergistically enhanced the anticancer activity of chemotherapeutic agents against cervical cancer HeLa cells. Furthermore, our study demonstrated that SB365 increased the phosphorylation of ERK and inhibited the phosphorylation of mTOR and p70S6K, suggesting that their roles in the effects of SB365 on autophagy. These results suggest that SB365 could be a promising adjuvant anticancer agent.

Hormesis is an adaptive response of living organisms to a moderate stress. However, its biomedical implication and molecular mechanisms remain to be intensively investigated. Panaxatriol saponins (PTS) is the major bioactive components extracted from Panax notoginseng, a widely used herbal medicine for cerebrovascular diseases. This study aims to examine the hormetic and neuroprotective effects of PTS in PC12 cells and zebrafish Parkinson’s disease (PD) models. Our results demonstrated that PTS stimulated PC12 cell growth by about 30% at low doses, while PTS at high doses inhibited cell growth, which is a typical hormetic effect. Moreover, we found that low dose PTS pretreatment significantly attenuated 6-OHDA-induced cytotoxicity and up-regulated PI3K/AKT/mTOR cell proliferation pathway and AMPK/SIRT1/FOXO3 cell survival pathway in PC12 cells. These results strongly suggested that neuroprotective effects of PTS may be attributable to the hormetic effect induced by PTS through activating adaptive response-related signaling pathways. Notably, low dose PTS could significantly prevent the 6-OHDA-induced dopaminergic neuron loss and improve the behavior movement deficiency in zebrafish, whereas relative high dose PTS exhibited neural toxicity, further supporting the hormetic and neuroprotective effects of PTS. This study indicates that PTS may have the potential in the development of future therapeutic medicines for PD.

Metabolomics is a comprehensive assessment of endogenous metabolites of a biological system in a holistic context. In this study, we evaluated the in vivo anti-melanoma activity of aqueous extract of Forsythiae Fructus (FAE) and globally explored the serum metabolome characteristics of B16-F10 melanoma-bearing mice. UPLC/Q-TOF MS combined with pattern recognition approaches were employed to examine the comprehensive metabolic signatures and differentiating metabolites. The results demonstrated that FAE exhibited remarkable antitumor activity against B16-F10 melanoma in C57BL/6 mice and restored the disturbed metabolic profile by tumor insult. We identified 17 metabolites which were correlated with the antitumor effect of FAE. Most of these metabolites are involved in glycerophospholipid metabolisms. Notably, several lysophosphatidylcholines (LysoPCs) significantly decreased in tumor model group, while FAE treatment restored the changes of these phospholipids to about normal condition. Moreover, we found that lysophosphatidylcholine acyltransferase 1 (LPCAT1) and autotaxin (ATX) were highly expressed in melanoma, and FAE markedly down-regulated their expression. These findings indicated that modulation of glycerophospholipid metabolisms may play a pivotal role in the growth of melanoma and the antitumor activity of FAE. Besides, our results suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma and other malignant tumors.

Curcumin (CUR) and berberine (BBR) are renowned natural compounds that exhibit potent anticancer activities through distinct molecular mechanisms. However, the anticancer capacity of either CUR or BBR is limited. This prompted us to investigate the chemopreventive potential of co-treatment of CUR and BBR against breast cancers. The results showed that CUR and BBR in combination synergistically inhibited the growth of both MCF-7 and MDA-MB-231 breast cancer cells than the compounds used alone. Further study confirmed that synergistic anti-breast cancer activities of co-treatment of these two compounds was through inducing more apoptosis and autophagic cell death (ACD). The co-treatment-induced apoptosis was caspase-dependent and through activating ERK pathways. Our data also demonstrated that co-treatment of CUR and BBR strongly up-regulated phosphorylation of JNK and Beclin1 and decreased phosphorylated Bcl-2. Inhibition of JNK by SP600125 markedly decreased LC3-II and Beclin1, restored phosphorylated Bcl-2 and reduced the cytotoxicity induced by the two compounds in combination. These results strongly suggested that JNK/Bcl-2/Beclin1 pathway played a key role in the induction of ACD in breast cancer cells by co-treatment of CUR and BBR. This study provides an insight into the potential application of curcumin and berberine in combination for the chemoprevention and treatment of breast cancers.

Berberine (BBR) is a renowned natural compound that exhibits potent neuroprotective activities. However, the cellular and molecular mechanisms are still unclear. Hormesis is an adaptive mechanism generally activated by mild oxidative stress to protect the cells from further damage. Many phytochemicals have been shown to induce hormesis. This study aims to investigate whether the neuroprotective activity of BBR is mediated by hormesis and the related signaling pathways in 6-OHDA-induced PC12 cells and zebrafish neurotoxic models. Our results demonstrated that BBR induced a typical hormetic response in PC12 cells, i.e. low dose BBR significantly increased the cell viability, while high dose BBR inhibited the cell viability. Moreover, low dose BBR protected the PC12 cells from 6-OHDA-induced cytotoxicity and apoptosis, whereas relatively high dose BBR did not show neuroprotective activity. The hormetic and neuroprotective effects of BBR were confirmed to be mediated by up-regulated PI3K/AKT/Bcl-2 cell survival and Nrf2/HO-1 antioxidative signaling pathways. In addition, low dose BBR markedly mitigated the 6-OHDA-induced dopaminergic neuron loss and behavior movement deficiency in zebrafish, while high dose BBR only slightly exhibited neuroprotective activities. These results strongly suggested that the neuroprotection of BBR were attributable to the hormetic mechanisms via activating cell survival and antioxidative signaling pathways. Keywords: Berberine, Hormesis, Neuroprotection, PC12 cells, Zebrafish

Background Paris polyphylla is an oriental folk medicine that has anticancer activities both in vivo and in vitro. Polyphyllin VII (PP7), a pennogenyl saponin from P. polyphylla has been found to exert strong anticancer activity. However, the underlying mechanisms are poorly understood. In the present study, the anticancer effect of polyphyllin VII against human liver cancer cells and the molecular mechanisms were investigated. Methods Cellular viability was measured by MTT assay. Apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential levels were evaluated using the InCell 2000 confocal microscope. The expression levels of apoptotic-related proteins were evaluated by Western blotting. Results PP7 strongly inhibited the cell growth and induced apoptosis and necrosis in hepatocellular carcinoma HepG2 cells. Meanwhile, PP7 up-regulated the levels of Bax/Bcl-2, cytochrome c, the cleaved forms of caspases-3, -8, -9, and poly (ADP-ribose) polymerase in a dose- and time-dependent manner, indicating that PP7 induced apoptosis in HepG2 cells through both intrinsic and extrinsic pathways. Moreover, PP7 provoked the production of intracellular ROS and the depolarization of mitochondrial membrane potential. Further analysis showed that PP7 significantly augmented the phosphorylation of JNK, ERK and p38, the major components of mitogen-activated protein kinase (MAPK) pathways, and the expressions of tumor suppressor proteins p53 and PTEN. In addition, PP7-induced apoptosis was remarkably attenuated by MAPK inhibitors and ROS inhibitor. Conclusions These results demonstrated that PP7 induced apoptotic cell death in HepG2 cells through both intrinsic and extrinsic pathways by promoting the generation of mitochondrial-mediated ROS and activating MAPK and PTEN/p53 pathways. Electronic supplementary material The online version of this article (doi:10.1186/s12906-016-1036-x) contains supplementary material, which is available to authorized users.