ABSTRACT
BACKGROUND: Chichoric acid (CA) is a major active ingredient found in chicory and Echinacea. As a derivative of caffeic acid, it has various pharmacological effects. PURPOSE: Due to the unclear etiology and disease mechanisms, effective treatment methods for ulcerative colitis (UC) are currently lacking. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and dextran sulfate sodium (DSS)-induced mouse UC models. METHODS: Folate-chicory acid liposome was prepared using the double emulsion ultrasonic method with the aim of targeting folate receptors specifically expressed on macrophages. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and DSS -induced mouse UC models. Furthermore, the effects of the liposomes on macrophage polarization and their underlying mechanisms in UC were explored. RESULTS: The average particle size of folate-chicory acid liposome was 120.4 ± 0.46 nm, with an encapsulation efficiency of 77.32 ± 3.19 %. The folate-chicory acid liposome could alleviate macrophage apoptosis induced by LPS, decrease the expression of inflammatory factors in macrophages, enhance the expression of anti-inflammatory factors, inhibit macrophage polarization towards the M1 phenotype, and mitigate cellular inflammation in vetro. In vivo test, folate-chicory acid liposome could attenuate clinical symptoms, increased colon length, reduced DAI scores, CMDI scores, and alleviated the severity of colonic histopathological damage in UC mice. Furthermore, it inhibited the polarization of macrophages towards the M1 phenotype in the colon and downregulated the TLR4/NF-κB signaling pathway, thereby ameliorating UC in mice. CONCLUSION: Folate-chicory acid liposome exhibited a uniform particle size distribution and high encapsulation efficiency. It effectively treated UC mice by inhibiting the polarization of macrophages towards the M1 phenotype in the colon and downregulating the TLR4/NF-κB signaling pathway.
Subject(s)
Caffeic Acids , Colitis, Ulcerative , Folic Acid , Lipopolysaccharides , Liposomes , Macrophages , NF-kappa B , Signal Transduction , Toll-Like Receptor 4 , Animals , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/chemically induced , Folic Acid/pharmacology , Folic Acid/chemistry , Folic Acid/analogs & derivatives , Toll-Like Receptor 4/metabolism , Mice , NF-kappa B/metabolism , Signal Transduction/drug effects , Macrophages/drug effects , Caffeic Acids/pharmacology , Caffeic Acids/chemistry , Male , RAW 264.7 Cells , Disease Models, Animal , Dextran Sulfate , Succinates/pharmacology , Succinates/chemistry , Mice, Inbred C57BL , Apoptosis/drug effects , Anti-Inflammatory Agents/pharmacologyABSTRACT
Ginseng (G) and Prepared Rehmannia Root (PRR) are commonly used in traditional Chinese medicine for blood supplementation. This study aimed to study G and PRR with different compatibility ratios changes in chemical composition and inhibition of cyclophosphamide-induced myelosuppression. HPLC was used to determine the chemical constituents of 13 ginsenosides, 5-hydroxymethylfurfural (5-HMF) and verbascoside in different proportions of G-PRR. Balb/c mice were injected intraperitoneally with cyclophosphamide (CTX) to induce bone marrow suppression. The effects of different proportions of G-PRR on peripheral blood, bone marrow nucleated cells, thymus and spleen index of myelosuppressed mice were analyzed. The results showed that the compatibility of G and PRR can promote the dissolution of ginsenosides, and the content of conventional ginsenosides decreased, and the content of rare ginsenosides increased. Different proportions of G-PRR increased the number of peripheral blood and bone marrow nucleated cells in cyclophosphamide-induced bone marrow suppression mice (p < 0.01), increased thymus index (p < 0.01), decreased spleen index (p < 0.01). Different proportions of G-PRR can improve the myelosuppression induced by cyclophosphamide in mice, and the combined effect of G-PRR is better than the single decoction of G and PRR. Among them, G-PRR 2 : 3 and G-PRR 1 : 2 were better than the other groups. These results indicate that different proportion of G-PRR can improve bone marrow suppression, and the combined decoction of G-PRR is better than the separate Decoction in improving bone marrow suppression. This improvement may be related to the changes of the substance basis and active ingredients of G-PRR.
Subject(s)
Bone Marrow/drug effects , Furaldehyde/analogs & derivatives , Ginsenosides/pharmacology , Glucosides/pharmacology , Panax/chemistry , Phenols/pharmacology , Rehmannia/chemistry , Animals , Antineoplastic Agents, Alkylating/administration & dosage , Cyclophosphamide/administration & dosage , Disease Models, Animal , Dose-Response Relationship, Drug , Furaldehyde/chemistry , Furaldehyde/pharmacology , Ginsenosides/chemistry , Glucosides/chemistry , Injections, Intraperitoneal , Male , Medicine, Chinese Traditional , Mice , Mice, Inbred BALB C , Molecular Structure , Phenols/chemistry , Plant Roots/chemistry , Structure-Activity RelationshipABSTRACT
OBJECTIVE: To study the changes of ginsenoside content in different proportion of Panax ginseng-Angelica sinensis (GA) co-decoction, and to explore the amelioration of hematopoietic function in mice after combined use of the two drugs. The active ingredient profiles in P. ginseng single decoction and co-decoction of GA were determined by high performance liquid chromatography (HPLC). The experimental pharmacology method was used to explore the effect of GA co-decoction on the hematopoietic function of chemotherapy mice. RESULTS: The active ingredient profiles of the co-decoction of GA significantly changed compared with those of the single decoction. Compared with GA1:0 (single decoction of Panax ginseng), the routine ginsenosides of all proportions of GA decreased significantly, but the proportion of rare ginsenosides increased significantly. The changes of contents of rare ginsenosides of GA were basically consistent with the trends of effects on the myelosuppression induced by CY. Compared with the model group, GA significantly increased the number of bone marrow nucleated cells, thymus index, peripheral blood leukocytes and platelets, and significantly reduced the spleen index. Moreover, GA could promote G1 phase bone marrow cells to enter the cell cycle, increase the proportion of S phase cells and G2/M phase cells, and increase the cell proliferation index. CONCLUSION: GA can ameliorate the hematopoietic function of mice after chemotherapy, and GA2:3, GA3:2 were the best, which may be due to the changes of the pharmacodynamic material basis of GA after compatibility. All these results implied that GA may be an ideal drug and food supplement for the treatment of toxic and side effects of chemotherapeutic drugs.
Subject(s)
Angelica sinensis/chemistry , Drugs, Chinese Herbal/therapeutic use , Ginsenosides/therapeutic use , Hematopoiesis/drug effects , Panax/chemistry , Animals , Drugs, Chinese Herbal/pharmacology , Ginsenosides/pharmacology , MiceABSTRACT
In this study, we aimed to investigate the effects of the combination of Panax ginseng and Ophiopogon japonicus (PG-OJ) herbs at different ratios on myelosuppression induced by chemotherapy. The myelosuppression model was established using an intraperitoneal injection of 100 mg kg-1 cyclophosphamide (CTX) in mice. The mice were administered the PG-OJ extract or Shengmaiyin (SMY) at different proportions (1 : 0, 1 : 1, 1 : 2, 2 : 1, 2 : 3, 3 : 2, and 0 : 1). The changes in the chemical composition caused by decocting the herbs together were analyzed by HPLC. The parameters i.e. the number of bone marrow nucleated cells and peripheral blood cells and the thymus and spleen indices were determined after administration. The results indicated that the co-decoction of PG and OJ, especially at the ratio of 2 : 3, was more conducive to the conversion of conventional ginsenosides (Rg1, Re, Rb1, Rg2, Rc, Rb2, Rb3 and Rd) to rare ginsenosides (Rg5, Rk3, S-Rg3, R-Rg3, Rk1 and Rh1) and the dissolution of ophiopogonin D. In addition, PG-OJ has an excellent synergistic effect on myelosuppression induced by CTX in mice. PG-OJ could significantly increase the numbers of the bone marrow nucleated cells and peripheral blood cells; moreover, it increased the thymus index and decreased the spleen index. The herb pair with a ratio of 2 : 3 showed the best therapeutic effect. By combining the results of the chemical composition changes and pharmacological activities, it can be concluded that rare ginsenosides and ophiopogonin D may be the main material basis of PG-OJ for the treatment of bone marrow suppression after chemotherapy.
Subject(s)
Antineoplastic Agents/toxicity , Cyclophosphamide/toxicity , Ophiopogon/chemistry , Panax/chemistry , Animals , Bone Marrow Cells/drug effects , Ginsenosides/chemistry , Male , Mice , Mice, Inbred BALB C , Phytotherapy , Random Allocation , Spleen , Thymus GlandABSTRACT
Ginsenoside compound K (CK) is not a ginsenoside that naturally exists in Panax ginseng Meyer. However, CK is a major metabolite of ginsenoside Rb1, Rb2, or Rc in the intestine under the effects of bacteria. In this study, we first investigated the effects of CK on myelosuppression in mice induced by cyclophosphamide (CTX). The respective quantities of white blood cells, blood platelets, and bone marrow nucleated cells (BMNCs) were determined to be 8.54 ± 0.91 (109/L), 850.90 ± 44.11 (109/L), and 1.45 ± 0.22 (109/L) in the CK-H group by detecting peripheral blood cells and BMNCs. CK-H and CK-L both increased the thymus index by up to 0.62 ± 0.06 (mg/g) and 0.52 ± 0.09 (mg/g), respectively, and significantly increased the yields of colony formation units-granulocyte monocyte and colony formation units-megakaryocytic. According to our study, CK could control apoptosis and promote cells to enter the normal cell cycle by the bcl-2/bax signaling pathway and MEK/ERK signaling pathway. Therefore, the BMNCs could proliferate and differentiate normally after entering the normal cell cycle. So the peripheral blood cells could show a trend of returning to normal. The recovery of peripheral blood cells resulting in the level of cytokines tended to normal. This process may be the mechanisms of CK on myelosuppression. This study provides a reference for ginseng in the treatment of myelosuppression.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Ginsenosides/pharmacology , Myeloid Cells/drug effects , Myelopoiesis/drug effects , Panax/chemistry , Animals , Apoptosis/drug effects , Blood Cells/cytology , Blood Cells/drug effects , Cell Cycle , Cells, Cultured , Male , Mice , Mice, Inbred BALB C , Myeloid Cells/cytology , Spleen/cytology , Spleen/drug effects , Thymus Gland/cytology , Thymus Gland/drug effectsABSTRACT
This study investigated the combination effects of the Acanthopanax senticosus - Ligustrum lucidum (AS-LL) herb pair on bone marrow suppression caused by chemotherapy. A bone marrow suppression model was established by intraperitoneal injection (i.p.) of cyclophosphamide (CTX, 100 mg/kg). The changes in chemical composition between the AS-LL decocted together and single were analyzed, and their effects on the bone marrow nucleated cells, peripheral blood, thymus and spleen indices, in vitro hematopoietic cell culture, ELISA and cell cycle were detected. The results showed that the contents of the main active components, such as salidroside, isofraxidin and specnuezhenide in the sample of AS-LL decocted together, increased significantly compared to singles. Moreover, AS-LL decocted together exhibited a significantly better therapeutic effect on myelosuppression induced by CTX than AS and LL alone. AS-LL decocted together significantly increased the number of bone marrow nucleated cells and displayed a good regulatory effect on peripheral blood (p < 0.01), while significantly increased the thymus index (p < 0.01) and decreased the spleen index (p < 0.01). AS-LL significantly promoted the formation of cell colonies (p < 0.05), the proliferation and differentiation of hematopoietic progenitor cells, and played a positive regulatory role in hematopoietic factors. AS-LL also reduced the proportion of G0/G1 cells, increased the ratio of S and G2/M cells, and increased the cell proliferation index (PI). All these results implied that AS-LL decocted together might be a promising food additives and therapeutic agent for myelosuppression induced by chemotherapy.