ABSTRACT
The strong human immunity and the associated toxicities of attenuated Salmonella severely limit the clinical use of Salmonella in tumour suppression. In the present study, we constructed an engineered VNP20009-DNase I strain and evaluated the synergistic effects of triptolide (TPL) and VNP20009-DNase I against melanoma in mice. Our results indicated that TPL could significantly inhibit the cell growth and cell migration and significantly enhanced the apoptosis rate of B16F10 cells in vitro. The in vivo results indicated that TPL markedly improved tumour colonisation of VNP20009-DNase I and led to a larger necrotic area in the melanoma. Moreover, the combination therapy significantly suppressed tumour volume and prolonged the life span of mice (P < 0.05) by upregulating the expression of Bcl-2/Bax and Caspase-3 and by downregulating the TLR4/NF-κB signalling, the expression of p-AKT/AKT and the production of proinflammatory factors. Therefore, the sound synergistic anti-tumour effects of TPL and VNP20009-DNase I indicate that the unconventional application of TPL and biological agents, approved by the China Food and Drug Administration (CFDA), can result in improved anti-cancer therapeutic outcomes.
Subject(s)
Antineoplastic Agents, Alkylating/administration & dosage , Combined Modality Therapy/methods , Deoxyribonuclease I/pharmacology , Diterpenes/pharmacology , Melanoma/therapy , Phenanthrenes/pharmacology , Salmonella/enzymology , Vaccines, DNA/administration & dosage , Animals , Antineoplastic Agents, Alkylating/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Deoxyribonuclease I/genetics , Disease Models, Animal , Drug Carriers/administration & dosage , Epoxy Compounds/pharmacology , Genetic Vectors , Humans , Mice , Models, Biological , Plasmids/administration & dosage , Salmonella/genetics , Salmonella Infections/microbiology , Treatment Outcome , Vaccines, DNA/pharmacologyABSTRACT
To minimize the waste of active ingredients present in herb residues, in the present study, probiotics of Bacillus subtilis, Aspergillus oryzae and Lactobacillus plantarum M3 were selected to reuse herb residues from Jianweixiaoshi tablets, and the therapeutic effects of the herb residue fermentation supernatant were evaluated using a spleendeficient mouse model. The results of the present study indicated that the fermentation supernatant may effectively improve the immunity of mice, as measured by body weight, spleen and thymus index, and inflammatory cytokines, including interleukin (IL)2, IL4 and interferonγ. The viable cell count and denaturing gradient gel electrophoresis results indicated that the fermentation supernatant markedly enhanced bacterial diversity and the number of lactobacilli in mouse intestines. Therefore, the combination of the Jianweixiaoshi herb residue and probiotics provided a novel method to reuse herb residues and may in the future contribute to the treatment of spleen deficiency.
Subject(s)
Culture Media, Conditioned/pharmacology , Fermentation , Probiotics/metabolism , Animals , Bacteria/metabolism , Biomarkers , Cytokines/metabolism , Inflammation Mediators/metabolism , Lactobacillus/metabolism , Mice , Splenectomy , TabletsABSTRACT
Environmental pollution caused by herb residues and the huge waste of medicinal ingredients contained in herb residues hinder the development of traditional Chinese medicine enterprises. To solve this problem, several probiotics were tested, and Lactobacillus plantarum (HM218749) was finally selected for the reuse of herb residues of Jianweixiaoshi tablets. A mouse model of Helicobacter pylori infection was developed to evaluate the anti-H. pylori infection activity of the herb residue fermentation supernatant using a urease activity test, histological imaging, an enzyme-linked immunosorbent assay (ELISA) and denaturing gel gradient electrophoresis (DGGE). The results demonstrated that the herb residue fermentation supernatant successfully inhibited urease activity, slowed cell infiltration in the gastric area and significantly reduced the production of interleukin-6 (IL-6), IL-8 and TNF-α in the treatment group (p<0.01). In addition, the DGGE results indicated that the herb residue fermentation supernatant was beneficial for the recovery of the disturbed microbiota in the infected model to the normal condition, in which L. gasseri (GU417842.1) and L. johnsonii (HQ828141.1) were dominant in all groups. Therefore, the probiotics exhibited strong potential for the development of herb residues in this study, and the products showed strong potential in curing H. pylori infections.
Subject(s)
Helicobacter Infections/drug therapy , Lactobacillus plantarum/metabolism , Plant Extracts/administration & dosage , Plant Extracts/metabolism , Plants, Medicinal/chemistry , Animals , China , Denaturing Gradient Gel Electrophoresis , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Fermentation , Histocytochemistry , Male , Mice , Mice, Inbred C57BL , Plant Extracts/chemistry , Treatment OutcomeABSTRACT
Residues from herbal medicine processing in pharmaceutical plants create a large amount of waste (herb residues), which consists mainly of environmental pollution and medicinal waste. In order to resolve this problem, probiotics of Bacillus (B.) subtilis, Aspergillus (A.) oryzae, and Lactobacillus (L.) plantarum M3 are selected to reuse herb residue of Jianweixiaoshi tablets (JT), and an antibiotic-associated diarrhea (AAD) mouse model was established to evaluate the therapeutic effects of the herb residue fermentation supernatant. Our results indicated that the fermentation supernatant had scavenged 77.8% of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 78% of O2â¢-, 36.7% of â¢OH, 39% of Fe2+ chelation, and 716 mg/L reducing power. The inhibition zones for Salmonella (S.) typhimurium, S. enteritidis, Shigella (Sh.) flexneri, Escherichia (E.) coli, Listeria (L.) monocytogenes, Sh. dysenteriae 301, and Staphylococcus (S.) aureus were 17, 14, 19, 18, 20, 19, and 20 mm, respectively. The in vivo results indicated that the fermentation supernatant resulted in a high diarrhea inhibition rate (56%, p < 0.05), greatly enhanced the disruption of bacterial diversity caused by antibiotics, and restored the dominant position of L. johnsonii in the treatment and recovery stages. Therefore, the combination of the herb residue and probiotics suggests a potential to explore conversion of these materials for the possible development of therapies for AAD.
