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Background Main bioactive constituents and pharmacological functions of ripened red ginseng berry (Panax ginseng Meyer) have been frequently reported. Yet, the research gap targeting the beneficial activities of transformed green ginseng berries has not reported elsewhere. Methods Ginsenosides of new green berry cultivar K-1 (GK-1) were identified by HPLC-QTOF/MS. Ginsenosides bioconversion in GK-1 by bgp1 enzyme was confirmed with HPLC and TLC. Then, mechanisms of GK-1 and β-glucosidase (bgp1) biotransformed GK-1 (BGK-1) were determined by Quantitative Reverse Transcription-Polymerase Chain Reaction and Western blot. Results GK-1 possesses highest ginsenosides especially ginsenoside-Re amongst seven ginseng cultivars including (Chunpoong, Huangsuk, Kumpoong, K-1, Honkaejong, Gopoong, and Yunpoong). Ginseng root’s biomass is not affected with the harvest of GK-1 at 3 weeks after flowering period. Then, Re is bio-converted into a promising pharmaceutical effect of Rg2 via bgp1. According to the results of cell assays, BGK-1 shows decrease of tyrosinase and melanin content in α-melanocyte-stimulating hormone challenged-murine melanoma B16 cells. BGK-1 which is comparatively more effective than GK-1 extract shows significant suppression of the nuclear factor (NF)-κB activation and inflammatory target genes, in LPS-stimulated RAW 264.7 cells. Conclusion These results reported effective whitening and anti-inflammatory of BGK-1 as compared to GK-1., Graphical abstract Image 1

Cisplatin, as one of the most effective chemotherapeutic agents, its clinical use is limited by serious side effect of nephrotoxicity. Cisplatin‐induced nephrotoxicity is closely related to apoptosis induction and activation of caspase. The present study aimed to explore the potential protective effect of ginsenoside Rk1 (Rk1), a rare ginsenoside generated during steaming ginseng, on cisplatin‐induced nephrotoxicity and the underlying mechanisms in human embryonic kidney 293 (HEK‐293) cells. Our results showed that the reduced cell viability induced by cisplatin could significantly recover by Rk1. Furthermore, glutathione (GSH) as an oxidative index, was elevated and the lipid peroxidation product malondialdehyde (MDA) was significantly decreased after Rk1 treatment compared to the cisplatin group. Additionally, Rk1 can also decrease the ROS fluorescence expression and increase the protein levels of nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) compared to the cisplatin group, which suggested a suppression of oxidative response. More importantly, the cisplatin‐induced elevated protein levels of Bax, cleaved caspase‐3, cleaved caspase‐9, and decreased protein level of Bcl‐2 were reversed after treatment with Rk1. Our results elucidated the possible protective mechanism of Rk1 for the first time, which may involve in its anti‐oxidation and anti‐apoptosis effects.

Animal placentae can be used as health-promoting food ingredients with various therapeutic efficacies, but their use is limited by their unpleasant odor and taste. This study aimed to investigate the possibility of deodorization of sheep placenta via yeast fermentation. A yeast strain was successfully isolated and identified as a novel Brettanomyces strain (Brettanomyces deamine kh3). The deodorizing efficacy of fermentation of the sheep placenta with B. deamine kh3 was evaluated by 42 panels, based on evaluation of preference, ranking, and aroma profiles, and compared with normal placenta and placenta fermented with B. bruxellensis. The results of the sensory evaluation indicated that fermentation of the sheep placenta with B. deamine kh3 may improve its palatability by increasing flavors such as that of grass (tree), rubber, and burnt, and by decreasing the odor and soy sauce flavor. Solid-phase microextraction-gas chromatography (SPME-GC) showed that major off-flavors in sheep placenta, such as ammonia, dimethyl disulfide, and 1,3-dioxolane, were completely diminished in the sheep placenta fermented with B. deamine kh3. This study presents those major volatile compounds, including 2-isobutyl\-4,4-dimethyl-1,3-dioxane, and 3-methyl-1-butanol, could be crucial in improving the palatability of the sheep placentae fermented with B. deamine kh3. This study provides a good starting point for the industrial application of a new deodorization method.

Background: In our previous study, Hibiscus syriacus leaf tissue was successfully cultivated in an optimized callus culture system, and subsequently extracted with 70% ethanol to prepare H. syriacus callus extract (HCE). The previous study suggested that the callus culture is useful method for obtaining the anti-inflammatory ingredients from H. syriacus. Purpose: In the present study, we aimed to investigate the effect of HCE on the colorectal cancer (CRC) and its underlying mechanism of action using HT-29 cells and thymus-deficient mice bearing HT-29 xenografts. Methods: The cytotoxicity of HCE was investigated by MTT and colonies formation. The underling mechanism by which HCE regulates specific proteins in HT-29 cells was evaluated by the proteomic analysis. These putative proteins were validated using qRT-PCR and immunoblotting analyses. Subsequently, oral administration of HCE for 15 days further evaluating the anti-tumor activity by mRNA and protein expressions levels and tumor histopathology. Results: Results of cell viability and colony formation assays revealed a significant cytotoxic effect of HCE at doses below 100 μg/mL against HT-29 cells, but not against normal cells. Through differential protein expression analysis, signaling pathways underlying anti-CRC activity were predicted in HCE-treated HT-29 cells: Notch signaling, cholesterol biosynthesis, and AMPK signaling pathways. qRT-PCR and immunoblotting analyses indicated that the cytotoxic effect of HCE against HT-29 cells might be associated with the suppression of Notch signaling, which positively contributes to cholesterol biosynthesis. To our knowledge, this can be presented as the first study to demonstrate the detailed relationship between Notch signaling and cholesterol-AMPK signaling. Our in vivo result further corroborated the in vitro finding that 100 and 200 mg/kg HCE for 15 days exerts its anti-cancer effect via Notch signaling-mediated suppression of cholesterol synthesis without systemic toxicity. Conclusion: Our findings can serve as a starting point for developing the novel anti-CRC agent using HCE, as a targeted medicine acting on regulating Notch signaling and cholesterol synthesis.

Background Ginsenoside Rh2 is well known for many pharmacological activities, such as anticancer, antidiabetes, antiinflammatory, and antiobesity properties. Glycosyltransferases (GTs) are ubiquitous enzymes present in nature and are widely used for the synthesis of oligosaccharides, polysaccharides, glycoconjugates, and novel derivatives. We aimed to synthesize new ginsenosides from Rh2 using the recombinant GT enzyme and investigate its cytotoxicity with diverse cell lines. Methods We have used a GT gene with 1,224-bp gene sequence cloned from Lactobacillus rhamnosus (LRGT) and then expressed in Escherichia coli BL21 (DE3). The recombinant GT protein was purified and demonstrated to transform Rh2 into two novel ginsenosides, and they were characterized by nuclear magnetic resonance (NMR) techniques and evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay. Results Two novel ginsenosides with an additional glucopyranosyl (6→1) and two additional glucopyranosyl (6→1) linked with the C-3 position of the substrate Rh2 were synthesized, respectively. Cell viability assay in the lung cancer (A549) cell line showed that glucosyl ginsenoside Rh2 inhibited cell viability more potently than ginsenoside Rg3 and Rh2 at a concentration of 10 μM. Furthermore, glucosyl ginsenoside Rh2 did not exhibit any cytotoxic effect in murine macrophage cells (RAW264.7), mouse embryo fibroblasts cells (3T3-L1), and skin cells (B16BL6) at a concentration of 10 μM compared with ginsenoside Rh2 and Rg3. Conclusion This is the first report on the synthesis of two novel ginsenosides, namely, glucosyl ginsenoside Rh2 and diglucosyl ginsenoside Rh2 from Rh2 by using recombinant GT isolated from L. rhamnosus. Moreover, diglucosyl ginsenoside Rh2 might be a new candidate for treatment of inflammation, obesity, and skin whiting, and especially for anticancer.

Background: Frequent overdose of paracetamol (APAP) has become the major cause of acute liver injury. The present study was designed to evaluate the potential protective effects of ginsenoside Rk1 on APAP-induced hepatotoxicity and investigate the underlying mechanisms for the first time. Methods: Mice were treated with Rk1 (10 mg/kg or 20 mg/kg) by oral gavage once per d for 7 d. On the 7th d, all mice treated with 250 mg/kg APAP exhibited severe liver injury after 24 h, and hepatotoxicity was assessed. Results: Our results showed that pretreatment with Rk1 significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor, and interleukin-1β compared with the APAP group. Meanwhile, hepatic antioxidants, including superoxide dismutase and glutathione, were elevated compared with the APAP group. In contrast, a significant decrease in levels of the lipid peroxidation product malondialdehyde was observed in the ginsenoside Rk1-treated group compared with the APAP group. These effects were associated with a significant increase of cytochrome P450 E1 and 4-hydroxynonenal levels in liver tissues. Moreover, ginsenoside Rk1 supplementation suppressed activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels, which was shown using western blotting analysis. Histopathological observation also revealed that ginsenoside Rk1 pretreatment significantly reversed APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress, such as 3-nitrotyrosine, were also inhibited after pretreatment with Rk1 compared with the APAP group. Conclusion: The results clearly suggest that the underlying molecular mechanisms in the hepatoprotection of ginsenoside Rk1 in APAP-induced hepatotoxicity may be due to its antioxidation, antiapoptosis, anti-inflammation, and antinitrative effects. Keywords: anti-inflammation, anti-apoptosis, APAP-induced hepatotoxicity, ginsenoside Rk1, oxidative stress

Background: Similar to the leaves of P. Quinquefolius, American ginseng berry (AGB) is another important part of P. Quinquefolius with alternative therapeutic potential. The liver protection capabilities of the former have been demonstrated previously, however, the later has not yet been evaluated. Purpose: Based on our previous observation, the present work was designed to evaluate the hepatic protective effects for novel mechanisms of AGB in acetaminophen (APAP)-induced liver injury in vivo. Study design/Methods: All mice were divided into four groups as follows: normal group, APAP group and APAP + AGB (150 mg/kg and 300 mg/kg) groups. AGB were orally administered for one week before exposure to APAP (250 mg/kg). Severe liver injury was observed and hepatotoxicity was evaluated after 24 h through evaluating the biochemical markers, protein expressions levels and liver histopathology. Results: Our study results clearly demonstrated that AGB pretreatment ameliorated APAP-induced hepatic injury as evidenced by decreasing plasma alanine aminotransferase (ALT), aspartate transaminase (AST), tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) compared to the APAP group. Western blotting analysis showed that pretreatment with AGB decreased the expressions levels of TNF-α and nuclear transcription factor-κB (NF-κB p65) in liver tissues. Meanwhile, the protein expression levels of caspases, cytochrome c, and Bax were elevated by AGB treatment for seven days, while the protein expression level of Bcl-2 was inhibited comparison with that in APAP group. Furthermore, supplement of AGB resulted in increase of superoxide dismutase (SOD) and glutathione (GSH), while decrease of malondialdehyde (MDA) content and the expression levels of 4-hydroxynonenal (4-HNE) and cytochrome P450 E1 (CYP2E1). The results of histopathological staining demonstrated that AGB pretreatment inhibited APAP-induced hepatocyte infiltration, congestion, and necrosis. Conclusion: The present study demonstrated that AGB pretreatment protected liver cells against APAP-induced hepatotoxicity through inhibition of oxidative stress, inflammation responses via TNF-α-mediated caspase-3/-8/-9 signaling pathways.

Biological applications of gold nanoparticles (AuNps) have potentially explored an efficient agent attributed to their biocompatibility and high efficiency in drug delivery. Our study applied an extract of Hibiscus syriacus L. callus (HCE) with a pioneer implementation on the induction of mass production. Bioactive compounds present in HCE were identified by Gas chromatography-mass spectrometry (GC-MS) and Liquid chromatography MS (LC-MS), wherein, the Denatonium was exclusively identifiable in HCE. Next, AuNps were synthesized and optimized using HCE (HCE-AuNps), and the comparison was conducted to evaluate the anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated macrophages. As per result, HCE-AuNps was reported to show a prominent reduction of pro-inflammatory cytokines and renovate the mitochondrial function through restoring the mitochondrial membrane potential changes, decreasing reactive oxygen species (ROS) accumulation, and recovering ATP contents, respectively. Furthermore, the immunoblotting of LC3b/a accumulation, and p62 rapid degradation revealed that HCE-AuNps could induce the autophagy as an intracellular response to reinforce alleviation of pro-inflammatory cytokines and mitochondria dysfunction. Besides, 740 Y-P (PI3K agonist) was used to verify that inhibiting autophagy could partially reverse HCE-AuNps suppressed mitochondrial dysfunction, and thus exacerbated inflammation, supporting a causal role for autophagy in the anti-inflammatory effect of HCE-AuNps. Taken together, we strongly anticipate that HCE-AuNps would act as a potential autophagy inducer for LPS-triggered macrophage's inflammation, providing a novel insight for biosynthetic nanoparticles in the treatment of mitochondria dysfunction and inflammation related diseases.

Although growing evidence has shown that ginseng (Panax ginseng C.A. Meyer.) exerts strong protective and preventive effects on cisplatin-induced side effects, including nephrotoxicity, ototoxicity and cardiotoxicity, the ameliorative effects of ginseng on intestinal damage caused by cisplatin are unknown to date. Red ginseng (RG), a major processed product of the roots of Panax ginseng C.A. Meyer, can be used to control chemotherapy drug-induced multiple toxicity. In the present work, an animal model of cisplatin-induced intestinal injury was established to evaluate the ameliorative effects of RG and their underlying molecular mechanism for the first time. The results showed that a single cisplatin injection (20 mg kg−1) leads to loss of body weight, shrinkage of the small intestine, and sharp increase of the intestinal function index of diamine oxidase (DAO). These symptoms were remarkably relieved after the administration of RG at 300 and 600 mg kg−1 for 10 continuous days, respectively. In addition, RG markedly reduced the increase in malondialdehyde (MDA) levels and the consumption of superoxide dismutase (SOD) and catalase (CAT) caused by cisplatin-induced oxidative stress. Furthermore, RG pretreatment dramatically improved the cisplatin-induced apoptosis of intestinal villous cells, irregular nuclear arrangement, ablation of crypt cells, and damage to the mechanical barrier. In this study, pharmacological methods have been used to prove that RG can inhibit cisplatin intestinal toxicity by activating the PI3K/AKT signaling pathway to inhibit apoptosis and by antagonizing the MAPK-mediated autophagy pathway.